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<div class="pre-content"><div><div class="bk_prnt"><p class="small">NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.</p><p>PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. </p></div><div class="iconblock clearfix whole_rhythm no_top_margin bk_noprnt"><a class="img_link icnblk_img" title="Table of Contents Page" href="/books/n/pdqcis/"><img class="source-thumb" src="/corehtml/pmc/pmcgifs/bookshelf/thumbs/th-pdqcis-lrg.png" alt="Cover of PDQ Cancer Information Summaries" height="100px" width="80px" /></a><div class="icnblk_cntnt eight_col"><h2>PDQ Cancer Information Summaries [Internet].</h2><a data-jig="ncbitoggler" href="#__NBK66038_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK66038_dtls__"><div>Bethesda (MD): <a href="http://www.cancer.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Cancer Institute (US)</a>; 2002-.</div></div><div class="half_rhythm"></div><div class="bk_noprnt"><form method="get" action="/books/n/pdqcis/" id="bk_srch"><div class="bk_search"><label for="bk_term" class="offscreen_noflow">Search term</label><input type="text" title="Search this book" id="bk_term" name="term" value="" data-jig="ncbiclearbutton" /> <input type="submit" class="jig-ncbibutton" value="Search this book" submit="false" style="padding: 0.1em 0.4em;" /></div></form></div></div></div></div></div>
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<div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><h1 id="_NBK66038_"><span class="title" itemprop="name">Adult Hodgkin Lymphoma Treatment (PDQ®)</span></h1><div class="subtitle whole_rhythm">Health Professional Version</div><p class="contrib-group"><span itemprop="author">PDQ Adult Treatment Editorial Board</span>.</p><p class="small">Published online: August 15, 2018.</p></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="_abs_rndgid_" itemprop="description"><p id="CDR0000062675__674">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult Hodgkin lymphoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.</p><p id="CDR0000062675__675">This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p></div><div id="CDR0000062675__1"><h2 id="_CDR0000062675__1_">General Information About Adult Hodgkin Lymphoma (HL)</h2><div id="CDR0000062675__470"><h3>Incidence and Mortality</h3><p id="CDR0000062675__331">Estimated new cases and deaths from HL in the United States in 2018:[<a class="bk_pop" href="#CDR0000062675_rl_1_1">1</a>]</p><ul id="CDR0000062675__332"><li class="half_rhythm"><div>New cases: 8,500.</div></li><li class="half_rhythm"><div>Deaths: 1,050.</div></li></ul><p id="CDR0000062675__3">More than 75% of all newly diagnosed patients with adult HL can be cured with combination chemotherapy and/or radiation therapy.[<a class="bk_pop" href="#CDR0000062675_rl_1_2">2</a>] Over the last five decades, U.S. national mortality has fallen more rapidly for adult HL than for any other malignancy.[<a class="bk_pop" href="#CDR0000062675_rl_1_2">2</a>]</p></div><div id="CDR0000062675__721"><h3>Anatomy </h3><div id="CDR0000062675__722" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Anatomy%20of%20the%20lymph%20system&p=BOOKS&id=519414_CDR0000533339.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK66038.13/bin/CDR0000533339.jpg" alt="Lymph system; drawing shows the lymph vessels and lymph organs including the lymph nodes, tonsils, thymus, spleen, and bone marrow. One inset shows the inside structure of a lymph node and the attached lymph vessels with arrows showing how the lymph (clear fluid) moves into and out of the lymph node. Another inset shows a close up of bone marrow with blood cells." class="tileshop" title="Click on image to zoom" /></a></div><div class="caption"><p>Anatomy of the lymph system.</p></div></div><p id="CDR0000062675__996">HL most frequently presents in lymph node groups above the diaphragm and/or in mediastinal lymph nodes. Involvement of Waldeyer's ring or tonsillar lymph glands is rarely seen.</p></div><div id="CDR0000062675__723"><h3>Risk Factors </h3><p id="CDR0000062675__724">Risk factors for adult HL include the following:</p><ul id="CDR0000062675__725"><li class="half_rhythm"><div>Being in early adulthood (aged 20–39 years) (most often) or late adulthood (aged 65 years and older) (a smaller increase).</div></li><li class="half_rhythm"><div>Being male.</div></li><li class="half_rhythm"><div>Having a previous infection with the Epstein-Barr virus in the teenage years or early childhood.</div></li><li class="half_rhythm"><div>Having a first-degree relative with HL.</div></li></ul></div><div id="CDR0000062675__726"><h3>Clinical Features</h3><p id="CDR0000062675__727">These and other signs and symptoms may be caused by adult HL or by other conditions:</p><ul id="CDR0000062675__728"><li class="half_rhythm"><div>Painless, swollen lymph nodes in the neck, axilla, or inguinal area.</div></li><li class="half_rhythm"><div>Fever defined as 38ºC or higher.</div></li><li class="half_rhythm"><div>Drenching and recurrent night sweats.</div></li><li class="half_rhythm"><div>Weight loss of 10% or more of baseline weight in the previous 6 months.</div></li><li class="half_rhythm"><div>Pruritus, especially after bathing or after ingesting alcohol.</div></li><li class="half_rhythm"><div>Fatigue.</div></li></ul><p id="CDR0000062675__729">Treatment of HL should relieve these symptoms within days. (Refer to the PDQ summaries on <a href="/books/n/pdqcis/CDR0000062742/">Hot Flashes and Night Sweats</a>, <a href="/books/n/pdqcis/CDR0000062748/">Pruritus</a>, and <a href="/books/n/pdqcis/CDR0000062734/">Fatigue</a> for more information about managing these symptoms.)</p></div><div id="CDR0000062675__730"><h3>Diagnostic Evaluation</h3><p id="CDR0000062675__917">Diagnostic evaluation of patients with lymphoma may include the following:</p><ol id="CDR0000062675__918"><li class="half_rhythm"><div>Biopsy (preferably excisional), with interpretation by a qualified pathologist.</div></li><li class="half_rhythm"><div>History, with special attention given to the presence and duration of fever, night sweats, and unexplained weight loss of 10% or more of body weight in the previous 6 months.</div></li><li class="half_rhythm"><div>Physical examination.</div></li><li class="half_rhythm"><div>Laboratory tests.<ul id="CDR0000062675__919"><li class="half_rhythm"><div>Complete blood cell count and platelet count.</div></li><li class="half_rhythm"><div>Erythrocyte sedimentation rate.</div></li><li class="half_rhythm"><div>Chemistry panel (electrolytes, blood urea nitrogen, creatinine, calcium, aspartate transaminase, alanine aminotransferase, bilirubin, and alkaline phosphatase) plus lactate dehydrogenase, uric acid, and phosphorus.</div></li></ul></div></li><li class="half_rhythm"><div>Radiographic examination<ul id="CDR0000062675__920"><li class="half_rhythm"><div>Computed tomography (CT) of the neck, chest, abdomen, and pelvis; or metabolic imaging (fluorine F 18-fludeoxyglucose positron emission tomography [PET]) with PET-CT.</div></li></ul></div></li><li class="half_rhythm"><div>HIV testing.</div></li><li class="half_rhythm"><div>Hepatitis B and C serology.</div></li></ol><p id="CDR0000062675__966">All stages of adult HL can be subclassified into A and B categories: B for those with defined general symptoms (described below) and A for those without B symptoms. The B designation is given to patients with any of the following symptoms:</p><ul id="CDR0000062675__967"><li class="half_rhythm"><div>Unexplained weight loss (more than 10% of body weight in the 6 months before diagnosis).</div></li><li class="half_rhythm"><div>Unexplained fever with temperatures above 38°C.</div></li><li class="half_rhythm"><div>Drenching and recurrent night sweats.</div></li></ul><p id="CDR0000062675__968">The most-significant B symptoms are fevers and weight loss. Night sweats alone do not confer an adverse prognosis.</p><p id="CDR0000062675__969">Pruritus as a systemic symptom remains controversial and is not considered a B symptom in the <a href="#CDR0000062675__739">Ann Arbor classification system</a>.</p></div><div id="CDR0000062675__645"><h3>Prognostic Factors</h3><p id="CDR0000062675__731">The prognosis for a given patient depends on several factors. The most important
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||
factors are the following:[<a class="bk_pop" href="#CDR0000062675_rl_1_3">3</a>-<a class="bk_pop" href="#CDR0000062675_rl_1_5">5</a>]</p><ul id="CDR0000062675__732"><li class="half_rhythm"><div>Presence or absence of systemic B symptoms.</div></li><li class="half_rhythm"><div>Stage of disease.</div></li><li class="half_rhythm"><div>Presence of large masses.</div></li><li class="half_rhythm"><div>Quality and suitability of the treatment administered.</div></li></ul><p id="CDR0000062675__733">Other important factors are:[<a class="bk_pop" href="#CDR0000062675_rl_1_3">3</a>-<a class="bk_pop" href="#CDR0000062675_rl_1_5">5</a>]</p><ul id="CDR0000062675__734"><li class="half_rhythm"><div>Age.</div></li><li class="half_rhythm"><div>Sex.</div></li><li class="half_rhythm"><div>Erythrocyte sedimentation rate.</div></li><li class="half_rhythm"><div>Hematocrit.</div></li><li class="half_rhythm"><div>Extent of abdominal involvement.</div></li><li class="half_rhythm"><div>Absolute number of nodal sites of involvement.</div></li></ul></div><div id="CDR0000062675__970"><h3>Follow-up</h3><p id="CDR0000062675__885">Recommendations for posttreatment follow-up are not evidence based, but a variety of opinions have been published for high-risk patients who present with advanced-stage disease or for patients who achieve less-than-complete remission by PET-CT scans at the end of therapy.[<a class="bk_pop" href="#CDR0000062675_rl_1_6">6</a>-<a class="bk_pop" href="#CDR0000062675_rl_1_9">9</a>] For patients at high risk of relapse, conventional CT scans are employed for screening to avoid the increased false-positive test results and increased radiation exposure of serial PET-CT scans.[<a class="bk_pop" href="#CDR0000062675_rl_1_10">10</a>]</p><p id="CDR0000062675__997">For patients with negative findings from a PET-CT scan at the end of therapy, routine scans are not advised because of the very-low risk of recurrence.[<a class="bk_pop" href="#CDR0000062675_rl_1_11">11</a>] Opportunistic scanning is applied when patients present with suspicious symptoms, physical findings, or laboratory test results.</p><p id="CDR0000062675__964">Among 6,840 patients enrolled in German Hodgkin Study Group (GHSG) trials, with a median follow-up of 10.3 years, 141 patients relapsed after 5 years, compared with 466 patients who relapsed within 5 years. Treatment-related adverse effects and late relapses may occur beyond 20 years of follow-up.[<a class="bk_pop" href="#CDR0000062675_rl_1_12">12</a>]</p></div><div id="CDR0000062675__757"><h3>Adverse Long-term Effects of Therapy </h3><p id="CDR0000062675__995">Patients who complete therapy for HL are at risk of developing long-term side effects, ranging from direct damage to organ function or the immune system to second malignancies. For the first 15 years after treatment, HL is the main cause of death. By 15 to 20 years after therapy, the cumulative mortality from a second malignancy, cardiovascular disease, or pulmonary fibrosis will exceed the cumulative mortality from HL.[<a class="bk_pop" href="#CDR0000062675_rl_1_13">13</a>-<a class="bk_pop" href="#CDR0000062675_rl_1_16">16</a>] This risk of developing a second malignancy is even higher for individuals with a family history of cancer.[<a class="bk_pop" href="#CDR0000062675_rl_1_17">17</a>]</p><div id="CDR0000062675__886"><h4>Second malignancies</h4><p id="CDR0000062675__945">Recommendations for screening for secondary malignancies or follow-up of long-term survivors are consensus based and not derived from randomized trials.[<a class="bk_pop" href="#CDR0000062675_rl_1_18">18</a>]</p><p id="CDR0000062675__887"><b>Hematologic cancers:</b></p><ul id="CDR0000062675__888"><li class="half_rhythm"><div>
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<b>Acute myelogenous leukemia (AML):</b> Acute nonlymphocytic leukemia may occur in patients treated with combined-modality therapy or with combination chemotherapy alone, especially with increased exposure to alkylating agents.[<a class="bk_pop" href="#CDR0000062675_rl_1_19">19</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_20">20</a>] <ul id="CDR0000062675__946"><li class="half_rhythm"><div>At 10 years after therapy with regimens containing MOPP (mechlorethamine, vincristine, procarbazine, and prednisone), the risk of AML is approximately 3%, with the peak incidence occurring 5 to 9 years after therapy.[<a class="bk_pop" href="#CDR0000062675_rl_1_19">19</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_20">20</a>] The risk of acute leukemia at 10 years after therapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) appears to be less than 1%.[<a class="bk_pop" href="#CDR0000062675_rl_1_21">21</a>] </div></li><li class="half_rhythm"><div>A population-based study of more than 35,000 survivors during a 30-year time span identified 217 patients who developed AML. The absolute excess risk (AER) was significantly higher for older patients (i.e., >35 years at diagnosis) than for younger survivors (AER, 9.9 vs. 4.2 per 10,000 patient years, <i>P</i> < .001).[<a class="bk_pop" href="#CDR0000062675_rl_1_22">22</a>]</div></li></ul></div></li><li class="half_rhythm"><div>
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<b>Non-Hodgkin lymphoma (NHL):</b> The risk of NHL is also increased, but this risk is not clearly related to the type or extent of treatment.[<a class="bk_pop" href="#CDR0000062675_rl_1_23">23</a>]</div></li></ul><div id="CDR0000062675__889"><h5>Solid tumors</h5><p id="CDR0000062675__769"> An increase in second solid tumors has also been observed,
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especially mesothelioma and cancers of the lung, breast, thyroid, bone/soft tissue, stomach, esophagus, colon and rectum, uterine cervix, and head and neck.[<a class="bk_pop" href="#CDR0000062675_rl_1_19">19</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_23">23</a>-<a class="bk_pop" href="#CDR0000062675_rl_1_30">30</a>]
|
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These tumors occur primarily after radiation therapy or with combined-modality
|
||
treatment, and approximately 75% occur within radiation ports. The risk of developing a second solid tumor (cumulative incidence of a second cancer) increases with time after treatment.</p><ul id="CDR0000062675__947"><li class="half_rhythm"><div>At 15-year
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follow-up, the risk is approximately 13%.[<a class="bk_pop" href="#CDR0000062675_rl_1_19">19</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_23">23</a>] </div></li><li class="half_rhythm"><div>At 20-year follow-up, the risk is approximately 17%.[<a class="bk_pop" href="#CDR0000062675_rl_1_31">31</a>] </div></li><li class="half_rhythm"><div>At 25-year follow-up, the risk is approximately 22%.[<a class="bk_pop" href="#CDR0000062675_rl_1_24">24</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_32">32</a>] </div></li><li class="half_rhythm"><div>At 40-year follow-up, the risk is approximately 48%.[<a class="bk_pop" href="#CDR0000062675_rl_1_33">33</a>]</div></li></ul><p id="CDR0000062675__890">In a cohort of 18,862 5-year survivors from 13 population-based registries, the younger patients had elevated risks for breast, colon, and rectal cancers for 10 to 25 years before the ages when routine screening would be recommended in the general population.[<a class="bk_pop" href="#CDR0000062675_rl_1_28">28</a>] Even with involved-field doses of 15 Gy to 25 Gy, sarcomas, breast cancers, and thyroid cancers occurred with similar incidence in young patients compared with those receiving higher-dose radiation.[<a class="bk_pop" href="#CDR0000062675_rl_1_31">31</a>]</p><p id="CDR0000062675__948">Lung cancer and breast cancer are among the most-common second solid tumors that develop after therapy for HL.</p><ul id="CDR0000062675__770"><li class="half_rhythm"><div><b>Lung cancer:</b> Lung
|
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cancer is seen with increased frequency, even after chemotherapy alone, and the
|
||
risk of this cancer increases with cigarette smoking.[<a class="bk_pop" href="#CDR0000062675_rl_1_34">34</a>-<a class="bk_pop" href="#CDR0000062675_rl_1_37">37</a>] In a retrospective Surveillance, Epidemiology, and End Results (SEER) analysis, stage-specific survival was decreased by 30% to 60% in HL survivors compared with patients with de novo non-small cell lung cancer.[<a class="bk_pop" href="#CDR0000062675_rl_1_38">38</a>] </div></li><li class="half_rhythm"><div><b>Breast cancer:</b> Breast cancer
|
||
is seen with increased frequency after radiation therapy or combined-modality
|
||
therapy.[<a class="bk_pop" href="#CDR0000062675_rl_1_24">24</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_25">25</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_27">27</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_39">39</a>-<a class="bk_pop" href="#CDR0000062675_rl_1_42">42</a>] The risk appears greatest for females treated with radiation
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before age 30 years, especially for girls close to menarche. The incidence of breast cancer increases substantially after 15 years
|
||
of posttherapy follow-up.[<a class="bk_pop" href="#CDR0000062675_rl_1_24">24</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_26">26</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_43">43</a>-<a class="bk_pop" href="#CDR0000062675_rl_1_46">46</a>]
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</div><div>In two case-control studies of 479 patients who developed breast cancer after therapy for HL, cumulative absolute risks for developing breast cancer were calculated as a function of radiation therapy dose and the use of chemotherapy.[<a class="bk_pop" href="#CDR0000062675_rl_1_47">47</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_48">48</a>] With a 30-year to 40-year follow-up, cumulative absolute risks of breast cancer with exposure to radiation range from 8.5% to 39.6%, depending on age at diagnosis. These cohort studies show a continued increase in cumulative excess risk of breast cancer beyond 20 years of follow-up.[<a class="bk_pop" href="#CDR0000062675_rl_1_47">47</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_48">48</a>]</div><div>In a nested case-control study and subsequent cohort study, patients who received both chemotherapy and radiation therapy had a statistically significant lower risk of developing breast cancer than did those treated with radiation therapy alone.[<a class="bk_pop" href="#CDR0000062675_rl_1_40">40</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_49">49</a>] Reaching early menopause with fewer than 10 years of intact ovarian function appeared to account for the reduction in risk among patients who received combined-modality therapy.[<a class="bk_pop" href="#CDR0000062675_rl_1_49">49</a>] Reduction of radiation volume also decreased the risk of breast cancer after HL.[<a class="bk_pop" href="#CDR0000062675_rl_1_49">49</a>] </div></li></ul><p id="CDR0000062675__772">Several studies suggest that
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||
splenic-field radiation therapy and splenectomy increase the risk of a
|
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treatment-related second cancer.[<a class="bk_pop" href="#CDR0000062675_rl_1_50">50</a>-<a class="bk_pop" href="#CDR0000062675_rl_1_52">52</a>]</p><p id="CDR0000062675__773">Late effects of autologous stem cell transplantation for failure of induction chemotherapy include second malignancies, hypothyroidism, hypogonadism, herpes zoster, depression, and cardiac disease.[<a class="bk_pop" href="#CDR0000062675_rl_1_53">53</a>]</p></div></div><div id="CDR0000062675__867"><h4>Other adverse long-term effects </h4><p id="CDR0000062675__949">Treatment for HL also affects the endocrine, cardiac, pulmonary, skeletal, and immune systems. Chronic fatigue can be a debilitating symptom for some long-term survivors.</p><p id="CDR0000062675__760"><b>Infertility:</b> A toxic effect that is primarily related to chemotherapy is infertility, usually after regimens containing MOPP or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone).[<a class="bk_pop" href="#CDR0000062675_rl_1_23">23</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_54">54</a>-<a class="bk_pop" href="#CDR0000062675_rl_1_56">56</a>] After six to eight cycles of BEACOPP, most men had testosterone levels within normal range; however, 82% of women younger than 30 years recovered menses (mostly within 12 months), but only 45% of women older than 30 years recovered menses.[<a class="bk_pop" href="#CDR0000062675_rl_1_57">57</a>] ABVD appears to spare long-term testicular and ovarian function.[<a class="bk_pop" href="#CDR0000062675_rl_1_55">55</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_58">58</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_59">59</a>]</p><p id="CDR0000062675__761"><b>Hypothyroidism:</b> Hypothyroidism is a late complication primarily related to radiation therapy.[<a class="bk_pop" href="#CDR0000062675_rl_1_60">60</a>-<a class="bk_pop" href="#CDR0000062675_rl_1_62">62</a>] Long-term survivors who receive radiation therapy to the neck are followed up with annual thyroid-stimulating hormone testing.</p><p id="CDR0000062675__762"><b>Cardiac disease:</b> A late complication primarily related to
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radiation therapy is cardiac disease, the risk of which may persist for 25 years after first treatment.[<a class="bk_pop" href="#CDR0000062675_rl_1_60">60</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_63">63</a>-<a class="bk_pop" href="#CDR0000062675_rl_1_68">68</a>] The AER of fatal cardiovascular disease ranges from 11.9 to 48.9 per 10,000 patient years and is mostly attributable to fatal myocardial infarction (MI).[<a class="bk_pop" href="#CDR0000062675_rl_1_63">63</a>-<a class="bk_pop" href="#CDR0000062675_rl_1_65">65</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_67">67</a>] In a cohort of 7,033 HL patients, MI mortality risk persisted for 25 years after first treatment with supradiaphragmatic radiation therapy (dependent on the details of treatment planning), doxorubicin, or vincristine.[<a class="bk_pop" href="#CDR0000062675_rl_1_67">67</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_68">68</a>] The use of subcranial blocking did not reduce the incidence of fatal MI in a retrospective review, perhaps because of the exposure of the proximal coronary arteries to radiation.[<a class="bk_pop" href="#CDR0000062675_rl_1_64">64</a>] Compared with a normal-matched population, HL patients treated with mediastinal radiation have been reported to be at increased risk of complications, especially during cardiac surgery.[<a class="bk_pop" href="#CDR0000062675_rl_1_69">69</a>] </p><p id="CDR0000062675__763"><b>Pulmonary impairment:</b> Impairment of
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pulmonary function may occur as a result of mantle-field radiation therapy; this
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impairment is not usually clinically evident, and recovery in pulmonary testing
|
||
often occurs after 2 to 3 years.[<a class="bk_pop" href="#CDR0000062675_rl_1_70">70</a>] Pulmonary toxic effects from bleomycin as used in ABVD are seen in patients older than 40 years.[<a class="bk_pop" href="#CDR0000062675_rl_1_71">71</a>] </p><p id="CDR0000062675__764"><b>Bone necrosis:</b> Avascular necrosis of bone has
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||
been observed in patients treated with chemotherapy and is most likely related
|
||
to corticosteroid therapy.[<a class="bk_pop" href="#CDR0000062675_rl_1_72">72</a>]</p><p id="CDR0000062675__765"><b>Bacterial sepsis:</b> Bacterial sepsis may occur rarely after
|
||
splenectomy performed during staging laparotomy for HL;[<a class="bk_pop" href="#CDR0000062675_rl_1_73">73</a>] it
|
||
is much more common in children than in adults. </p><p id="CDR0000062675__766"><b>Fatigue:</b> Fatigue is a commonly reported symptom of patients who have completed
|
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chemotherapy and radiation therapy. In a case-control study design, a majority of HL
|
||
survivors reported significant fatigue lasting for more than 6 months after
|
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therapy, compared with age-matched controls. Quality-of-life questionnaires given to 5,306 patients on GHSG trials showed that 20% of patients complained of severe fatigue 5 years after therapy, and those patients had significantly increased problems with employment and financial stability.[<a class="bk_pop" href="#CDR0000062675_rl_1_74">74</a>,<a class="bk_pop" href="#CDR0000062675_rl_1_75">75</a>]
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(Refer to the PDQ summary on <a href="/books/n/pdqcis/CDR0000062734/">Fatigue</a> for more information about managing fatigue.)</p></div></div><div id="CDR0000062675__547"><h3>Related Summaries</h3><p id="CDR0000062675__548">Other PDQ summaries containing information related to Hodgkin lymphoma include the following:</p><ul id="CDR0000062675__549"><li class="half_rhythm"><div><a href="/books/n/pdqcis/CDR0000062933/">Childhood Hodgkin Lymphoma Treatment</a></div></li></ul></div><div id="CDR0000062675_rl_1"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062675_rl_1_1">American Cancer Society: Cancer Facts and Figures 2018. Atlanta, Ga: American Cancer Society, 2018. <a href="https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online</a>. Last accessed August 3, 2018.</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_2">Brenner H, Gondos A, Pulte D: Ongoing improvement in long-term survival of patients with Hodgkin disease at all ages and recent catch-up of older patients. Blood 111 (6): 2977-83, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18096762" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18096762</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_3">American Cancer Society: Cancer Facts and Figures 2007. 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[<a href="https://pubmed.ncbi.nlm.nih.gov/16234521" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16234521</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_55">van der Kaaij MA, Heutte N, Le Stang N, et al.: Gonadal function in males after chemotherapy for early-stage Hodgkin's lymphoma treated in four subsequent trials by the European Organisation for Research and Treatment of Cancer: EORTC Lymphoma Group and the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol 25 (19): 2825-32, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17515571" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17515571</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_56">Scholz M, Engert A, Franklin J, et al.: Impact of first- and second-line treatment for Hodgkin's lymphoma on the incidence of AML/MDS and NHL--experience of the German Hodgkin's Lymphoma Study Group analyzed by a parametric model of carcinogenesis. Ann Oncol 22 (3): 681-8, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/20720088" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20720088</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_57">Behringer K, Mueller H, Goergen H, et al.: Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials. J Clin Oncol 31 (2): 231-9, 2013. [<a href="https://pubmed.ncbi.nlm.nih.gov/23150709" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23150709</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_58">Viviani S, Santoro A, Ragni G, et al.: Pre- and post-treatment testicular dysfunction in Hodgkin's disease (HD). [Abstract] Proceedings of the American Society of Clinical Oncology 7: A-877, 227, 1988.</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_59">van der Kaaij MA, Heutte N, Meijnders P, et al.: Premature ovarian failure and fertility in long-term survivors of Hodgkin's lymphoma: a European Organisation for Research and Treatment of Cancer Lymphoma Group and Groupe d'Etude des Lymphomes de l'Adulte Cohort Study. J Clin Oncol 30 (3): 291-9, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/22184372" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22184372</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_60">Tarbell NJ, Thompson L, Mauch P: Thoracic irradiation in Hodgkin's disease: disease control and long-term complications. Int J Radiat Oncol Biol Phys 18 (2): 275-81, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2105920" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2105920</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_61">Hancock SL, Cox RS, McDougall IR: Thyroid diseases after treatment of Hodgkin's disease. N Engl J Med 325 (9): 599-605, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1861693" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1861693</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_62">Cella L, Conson M, Caterino M, et al.: Thyroid V30 predicts radiation-induced hypothyroidism in patients treated with sequential chemo-radiotherapy for Hodgkin's lymphoma. Int J Radiat Oncol Biol Phys 82 (5): 1802-8, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/21514076" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21514076</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_63">Reinders JG, Heijmen BJ, Olofsen-van Acht MJ, et al.: Ischemic heart disease after mantlefield irradiation for Hodgkin's disease in long-term follow-up. Radiother Oncol 51 (1): 35-42, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10386715" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10386715</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_64">Hancock SL, Tucker MA, Hoppe RT: Factors affecting late mortality from heart disease after treatment of Hodgkin's disease. JAMA 270 (16): 1949-55, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8411552" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8411552</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_65">Heidenreich PA, Schnittger I, Strauss HW, et al.: Screening for coronary artery disease after mediastinal irradiation for Hodgkin's disease. J Clin Oncol 25 (1): 43-9, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17194904" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17194904</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_66">Dabaja B, Cox JD, Buchholz TA: Radiation therapy can still be used safely in combined modality approaches in patients with Hodgkin's lymphoma. J Clin Oncol 25 (1): 3-5, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17194900" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17194900</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_67">Swerdlow AJ, Higgins CD, Smith P, et al.: Myocardial infarction mortality risk after treatment for Hodgkin disease: a collaborative British cohort study. J Natl Cancer Inst 99 (3): 206-14, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17284715" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17284715</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_68">van Nimwegen FA, Schaapveld M, Cutter DJ, et al.: Radiation Dose-Response Relationship for Risk of Coronary Heart Disease in Survivors of Hodgkin Lymphoma. J Clin Oncol 34 (3): 235-43, 2016. [<a href="https://pubmed.ncbi.nlm.nih.gov/26573075" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26573075</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_69">Galper SL, Yu JB, Mauch PM, et al.: Clinically significant cardiac disease in patients with Hodgkin lymphoma treated with mediastinal irradiation. Blood 117 (2): 412-8, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/20858859" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20858859</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_70">Horning SJ, Adhikari A, Rizk N, et al.: Effect of treatment for Hodgkin's disease on pulmonary function: results of a prospective study. J Clin Oncol 12 (2): 297-305, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7509383" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7509383</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_71">Martin WG, Ristow KM, Habermann TM, et al.: Bleomycin pulmonary toxicity has a negative impact on the outcome of patients with Hodgkin's lymphoma. J Clin Oncol 23 (30): 7614-20, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/16186594" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16186594</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_72">Prosnitz LR, Lawson JP, Friedlaender GE, et al.: Avascular necrosis of bone in Hodgkin's disease patients treated with combined modality therapy. Cancer 47 (12): 2793-7, 1981. [<a href="https://pubmed.ncbi.nlm.nih.gov/7260869" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7260869</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_73">Schimpff SC, O'Connell MJ, Greene WH, et al.: Infections in 92 splenectomized patients with Hodgkin's disease. A clinical review. Am J Med 59 (5): 695-701, 1975. [<a href="https://pubmed.ncbi.nlm.nih.gov/1200037" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1200037</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_74">Behringer K, Goergen H, Müller H, et al.: Cancer-Related Fatigue in Patients With and Survivors of Hodgkin Lymphoma: The Impact on Treatment Outcome and Social Reintegration. J Clin Oncol 34 (36): 4329-4337, 2016. [<a href="https://pubmed.ncbi.nlm.nih.gov/27998235" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27998235</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1_75">Loge JH, Abrahamsen AF, Ekeberg O, et al.: Hodgkin's disease survivors more fatigued than the general population. J Clin Oncol 17 (1): 253-61, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10458240" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10458240</span></a>]</div></li></ol></div></div><div id="CDR0000062675__295"><h2 id="_CDR0000062675__295_">Cellular Classification of Adult HL</h2><p id="CDR0000062675__6">Pathologists currently use the World Health Organization (WHO) modification of
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the Revised European-American Lymphoma (REAL) classification for the histologic
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classification of adult Hodgkin lymphoma (HL).[<a class="bk_pop" href="#CDR0000062675_rl_295_1">1</a>,<a class="bk_pop" href="#CDR0000062675_rl_295_2">2</a>]
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</p><div id="CDR0000062675__179"><h3>WHO Modification of the REAL Classification</h3><ul id="CDR0000062675__9"><li class="half_rhythm"><div class="half_rhythm">Classic HL.<dl id="CDR0000062675__188" class="temp-labeled-list"><dt>-</dt><dd><p class="no_top_margin">Nodular sclerosis HL.
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</p></dd><dt>-</dt><dd><p class="no_top_margin">Mixed-cellularity HL.</p></dd><dt>-</dt><dd><p class="no_top_margin">Lymphocyte-depleted HL.
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Among 10,019 patients who underwent central expert pathology review for the German Hodgkin Study Group, 84 patients (<1%) were identified as having lymphocyte-depleted classic HL.[<a class="bk_pop" href="#CDR0000062675_rl_295_3">3</a>] These patients presented more frequently with advanced-stage HL and <a href="#CDR0000062675__966">B symptoms</a>.</p></dd><dt>-</dt><dd><p class="no_top_margin">Lymphocyte-rich classic HL.</p></dd></dl></div></li><li class="half_rhythm"><div class="half_rhythm">Nodular lymphocyte–predominant HL (NLPHL). NLPHL is a clinicopathologic entity of B-cell origin that is distinct from classic HL.[<a class="bk_pop" href="#CDR0000062675_rl_295_4">4</a>-<a class="bk_pop" href="#CDR0000062675_rl_295_6">6</a>] </div><div class="half_rhythm">The typical immunophenotype for classic HL is CD15+, CD20-, CD30+, CD45-, while the profile for lymphocyte-predominant disease is CD15-, CD20+, CD30-, CD45+.</div></li></ul></div><div id="CDR0000062675_rl_295"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062675_rl_295_1">Lukes RJ, Craver LF, Hall TC, et al.: Report of the Nomenclature Committee. Cancer Res 26 (1): 1311, 1966.</div></li><li><div class="bk_ref" id="CDR0000062675_rl_295_2">Harris NL: Hodgkin's lymphomas: classification, diagnosis, and grading. Semin Hematol 36 (3): 220-32, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10462322" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10462322</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_295_3">Klimm B, Franklin J, Stein H, et al.: Lymphocyte-depleted classical Hodgkin's lymphoma: a comprehensive analysis from the German Hodgkin study group. J Clin Oncol 29 (29): 3914-20, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/21911729" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21911729</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_295_4">von Wasielewski R, Mengel M, Fischer R, et al.: Classical Hodgkin's disease. Clinical impact of the immunophenotype. Am J Pathol 151 (4): 1123-30, 1997. [<a href="/pmc/articles/PMC1858022/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1858022</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/9327746" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9327746</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_295_5">Bodis S, Kraus MD, Pinkus G, et al.: Clinical presentation and outcome in lymphocyte-predominant Hodgkin's disease. J Clin Oncol 15 (9): 3060-6, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9294468" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9294468</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_295_6">Orlandi E, Lazzarino M, Brusamolino E, et al.: Nodular lymphocyte predominance Hodgkin's disease: long-term observation reveals a continuous pattern of recurrence. Leuk Lymphoma 26 (3-4): 359-68, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9322899" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9322899</span></a>]</div></li></ol></div></div><div id="CDR0000062675__12"><h2 id="_CDR0000062675__12_">Stage Information for Adult HL</h2><p id="CDR0000062675__477">Clinical staging
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for patients with adult Hodgkin lymphoma (HL) includes the following: </p><ul id="CDR0000062675__972"><li class="half_rhythm"><div>Physical examination and history.</div></li><li class="half_rhythm"><div>Laboratory studies (including
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sedimentation rate).</div></li><li class="half_rhythm"><div>Thoracic and abdominal/pelvic computerized tomographic
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||
(CT) scans with or without positron emission tomography (PET).[<a class="bk_pop" href="#CDR0000062675_rl_12_1">1</a>] PET scans combined with CT scans have become the standard imaging for clinical staging.[<a class="bk_pop" href="#CDR0000062675_rl_12_2">2</a>]</div></li></ul><p id="CDR0000062675__869">Staging laparotomy is no longer recommended and
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||
should be considered only when the results will allow substantially less
|
||
treatment. Staging laparotomy should not be done in patients who require chemotherapy. If the laparotomy is required for treatment decisions, the risks
|
||
of potential morbidity should be considered.[<a class="bk_pop" href="#CDR0000062675_rl_12_3">3</a>-<a class="bk_pop" href="#CDR0000062675_rl_12_6">6</a>]</p><p id="CDR0000062675__939">Bone marrow involvement occurs in 5% of patients; marrow involvement is more prevalent in the context of constitutional <a href="#CDR0000062675__966">B symptoms</a> and anemia, leukopenia, or thrombocytopenia. In a retrospective review and meta-analysis of 955 patients in nine studies, fewer than 2% of patients with positive bone marrow biopsy results had only stage I or stage II disease on PET-CT scans.[<a class="bk_pop" href="#CDR0000062675_rl_12_7">7</a>] Omission of the bone marrow biopsy for PET-CT–designated early-stage patients did not change treatment selection.[<a class="bk_pop" href="#CDR0000062675_rl_12_7">7</a>] In addition, focal skeletal bone lesions on PET-CT predicted bone marrow involvement with a 96.9% (93.0%–99.08%) sensitivity and 99.7% (98.9%–100%) specificity.[<a class="bk_pop" href="#CDR0000062675_rl_12_7">7</a>] For these reasons, PET-CT has replaced bone marrow biopsy in the clinical staging of newly diagnosed HL.</p><p id="CDR0000062675__940">Massive mediastinal disease has been defined by the Cotswolds meeting as a thoracic ratio of maximum transverse mass diameter of 33% or more of the internal transverse thoracic diameter measured at the T5/6 intervertebral disc level on chest radiography.[<a class="bk_pop" href="#CDR0000062675_rl_12_1">1</a>] Some investigators have designated a lymph node mass measuring 10 cm or more in greatest dimension as massive disease.[<a class="bk_pop" href="#CDR0000062675_rl_12_8">8</a>] Other investigators use a measurement of the maximum width of the mediastinal mass divided by the maximum intrathoracic diameter.[<a class="bk_pop" href="#CDR0000062675_rl_12_9">9</a>]</p><p id="CDR0000062675__19">The E designation is used when well-localized extranodal lymphoid malignancies
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||
arise in or extend to tissues beyond, but near, the major lymphatic aggregates.
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Stage IV refers to disease that is diffusely spread throughout an extranodal
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site, such as the liver. If pathologic proof of involvement of one or more
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extralymphatic sites has been documented, the symbol for the site of
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involvement, followed by a plus sign (+), is listed.
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||
</p><div id="CDR0000062675__180" class="table"><h3><span class="title">Table 1. Notations for Identifying Sites </span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK66038.13/table/CDR0000062675__180/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062675__180_lrgtbl__"><table class="no_top_margin"><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">N = nodes</td><td colspan="1" rowspan="1" style="vertical-align:top;">H = liver </td><td colspan="1" rowspan="1" style="vertical-align:top;">L = lung</td><td colspan="1" rowspan="1" style="vertical-align:top;"> M = bone marrow</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">S = spleen</td><td colspan="1" rowspan="1" style="vertical-align:top;"> P = pleura</td><td colspan="1" rowspan="1" style="vertical-align:top;">O = bone</td><td colspan="1" rowspan="1" style="vertical-align:top;"> D = skin</td></tr></tbody></table></div></div><div id="CDR0000062675__739"><h3>Ann Arbor Classification System</h3><p id="CDR0000062675__601">The staging classification that is currently used for HL was adopted in 1971 at the Ann Arbor Conference,[<a class="bk_pop" href="#CDR0000062675_rl_12_10">10</a>] with some modifications 18 years later from the Cotswolds meeting.[<a class="bk_pop" href="#CDR0000062675_rl_12_1">1</a>] The American Joint Committee on Cancer (AJCC) has adopted the Ann Arbor classification system to classify the anatomic extent of disease in adult HL.[<a class="bk_pop" href="#CDR0000062675_rl_12_11">11</a>] </p><div id="CDR0000062675__532" class="table"><h3><span class="title">Table 2. Anatomic Stage/Prognostic Groups<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK66038.13/table/CDR0000062675__532/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062675__532_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Stage</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Description</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">Illustration</th></tr></thead><tbody><tr><td colspan="1" rowspan="2" style="text-align:center;vertical-align:top;">I</td><td colspan="1" rowspan="1" style="vertical-align:top;">Involvement of a single lymphatic site (i.e., nodal region, Waldeyer ring, thymus or spleen) (I).</td><td colspan="1" rowspan="2" style="vertical-align:top;"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Image%20CDR0000641792&p=BOOKS&id=519414_CDR0000641792.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK66038.13/bin/CDR0000641792.jpg" alt="Stage I adult Hodgkin lymphoma; drawing shows cancer in one lymph node group above the diaphragm. An inset shows a lymph node with a lymph vessel, an artery, and a vein. Lymphoma cells containing cancer are shown in the lymph node." class="tileshop" title="Click on image to zoom" /></a></div></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Localized involvement of a single extralymphatic organ or site in the absence of any lymph node involvement (IE)<sup>b</sup> (rare in Hodgkin lymphoma).</td></tr><tr><td colspan="1" rowspan="2" style="text-align:center;vertical-align:top;">II</td><td colspan="1" rowspan="1" style="vertical-align:top;">Involvement of ≥2 lymph node regions on the same side of the diaphragm (II).</td><td colspan="1" rowspan="2" style="vertical-align:top;"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Image%20CDR0000641793&p=BOOKS&id=519414_CDR0000641793.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK66038.13/bin/CDR0000641793.jpg" alt="Stage II adult Hodgkin lymphoma; drawing shows cancer in lymph node groups above and below the diaphragm. An inset shows a lymph node with a lymph vessel, an artery, and a vein. Lymphoma cells containing cancer are shown in the lymph node." class="tileshop" title="Click on image to zoom" /></a></div><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Image%20CDR0000641794&p=BOOKS&id=519414_CDR0000641794.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK66038.13/bin/CDR0000641794.jpg" alt="Stage IIE adult Hodgkin lymphoma; drawing shows cancer in one lymph node group above the diaphragm and in the left lung. An inset shows a lymph node with a lymph vessel, an artery, and a vein. Lymphoma cells containing cancer are shown in the lymph node." class="tileshop" title="Click on image to zoom" /></a></div></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Localized involvement of a single extralymphatic organ or site in association with regional lymph node involvement with or without involvement of other lymph node regions on the same side of the diaphragm (IIE).<sup>c</sup></td></tr><tr><td colspan="1" rowspan="1" style="text-align:center;vertical-align:top;"> III</td><td colspan="1" rowspan="1" style="vertical-align:top;">Involvement of lymph node regions on both sides of the diaphragm (III), which also may be accompanied by extralymphatic extension in association with adjacent lymph node involvement (IIIE) or by involvement of the spleen (IIIS) or both (IIIE, S). <sup>d</sup></td><td colspan="1" rowspan="1" style="vertical-align:top;"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Image%20CDR0000641795&p=BOOKS&id=519414_CDR0000641795.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK66038.13/bin/CDR0000641795.jpg" alt="Stage III adult Hodgkin lymphoma; drawing shows cancer in lymph node groups above and below the diaphragm, in the left lung, and in the spleen. An inset shows a lymph node with a lymph vessel, an artery, and a vein. Lymphoma cells containing cancer are shown in the lymph node." class="tileshop" title="Click on image to zoom" /></a></div></td></tr><tr><td colspan="1" rowspan="3" style="text-align:center;vertical-align:top;"> IV</td><td colspan="1" rowspan="1" style="vertical-align:top;">Diffuse or disseminated involvement of one or more extralymphatic organs, with or without associated lymph node involvement.</td><td colspan="1" rowspan="3" style="vertical-align:top;"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Image%20CDR0000641796&p=BOOKS&id=519414_CDR0000641796.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img src="/books/NBK66038.13/bin/CDR0000641796.jpg" alt="Stage IV adult Hodgkin lymphoma; drawing shows cancer in the liver, the left lung, and in one lymph node group below the diaphragm. The brain and pleura are also shown. One inset shows a close-up of cancer spreading through lymph nodes and lymph vessels to other parts of the body. Lymphoma cells containing cancer are shown inside one lymph node. Another inset shows cancer cells in the bone marrow." class="tileshop" title="Click on image to zoom" /></a></div></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Isolated extralymphatic organ involvement in the absence of adjacent regional lymph node involvement, but in conjunction with disease in distant site(s).</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Includes any involvement of the liver or bone marrow, lungs (other than by direct extension from another site), or cerebrospinal fluid.</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin"><sup>a</sup>Reprinted with permission from AJCC: Hodgkin and non-Hodgkin lymphomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 607-11.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>b</sup>Involvement of extralymphatic sites is designated by the letter E.</p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>c</sup>The number of regions involved may be indicated by an arabic numeral, as in, for example, II<sub>3</sub>. </p></div></dd><dt></dt><dd><div><p class="no_margin"><sup>d</sup>Splenic involvement is designated by the letter <i>S</i>. </p></div></dd></dl></div></div></div></div><div id="CDR0000062675__31"><h3>Prognostic Groups</h3><p id="CDR0000062675__873">Many investigators and many new clinical trials employ a clinical staging system that divides patients into three major groups that are also useful for the clinician:[<a class="bk_pop" href="#CDR0000062675_rl_12_12">12</a>] </p><ul id="CDR0000062675__973"><li class="half_rhythm"><div>Early favorable.</div></li><li class="half_rhythm"><div>Early unfavorable.</div></li><li class="half_rhythm"><div>Advanced.</div></li></ul><p id="CDR0000062675__974">The group assignment depends on:</p><ul id="CDR0000062675__941" class="simple-list"><li class="half_rhythm"><div>Whether the patient has early or advanced disease.</div></li><li class="half_rhythm"><div>The type and number of adverse prognostic factors present.</div></li></ul><p id="CDR0000062675__874"><b>Early-stage adverse prognostic factors:</b></p><ul id="CDR0000062675__875"><li class="half_rhythm"><div>Large mediastinal mass (>33% of the thoracic width on chest x-ray, ≥10 cm on CT scan).</div></li><li class="half_rhythm"><div> Extranodal involvement.</div></li><li class="half_rhythm"><div> Elevated erythrocyte sedimentation rate (>30 mm/h for <a href="#CDR0000062675__966">B stage [symptoms]</a>, >50 mm/h for <a href="#CDR0000062675__966">A stage [symptoms]</a>).</div></li><li class="half_rhythm"><div> Involvement of three or more lymph node areas.</div></li><li class="half_rhythm"><div> Presence of <a href="#CDR0000062675__966">B symptoms</a>.</div></li></ul><p id="CDR0000062675__876"><b>Early favorable group:</b> Clinical stage I or II without any of the adverse prognostic factors listed above.</p><p id="CDR0000062675__877"><b>Early unfavorable group:</b> Clinical stage I or II with one or more of the adverse prognostic factors listed above.</p><p id="CDR0000062675__878"><b>Advanced-stage adverse prognostic factors:</b></p><p id="CDR0000062675__879">For patients with advanced-stage HL, the International Prognostic Factors Project on Advanced Hodgkin's Disease developed the International Prognostic Index with a score that is based on the following seven adverse prognostic factors:[<a class="bk_pop" href="#CDR0000062675_rl_12_13">13</a>]</p><ul id="CDR0000062675__880"><li class="half_rhythm"><div> Albumin level lower than 4.0 g/dL.</div></li><li class="half_rhythm"><div> Hemoglobin level lower than 10.5 g/dL. </div></li><li class="half_rhythm"><div> Male sex.</div></li><li class="half_rhythm"><div> Age 45 years or older.</div></li><li class="half_rhythm"><div> Stage IV disease.</div></li><li class="half_rhythm"><div> White blood cell (WBC) count of 15,000/mm<sup>3</sup> or higher.</div></li><li class="half_rhythm"><div> Absolute lymphocytic count lower than 600/mm<sup>3</sup> or lymphocyte count higher than 8% of the total WBC count.</div></li></ul><p id="CDR0000062675__881"><b>Advanced group:</b> Clinical stage III or IV with up to three of the adverse risk factors listed above. Patients with advanced disease have a 60% to 80% freedom from progression of disease at 5 years from treatment with first-line chemotherapy.[<a class="bk_pop" href="#CDR0000062675_rl_12_13">13</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335158/" class="def">Level of evidence: 3iiiDiii</a>]</p></div><div id="CDR0000062675_rl_12"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062675_rl_12_1">Lister TA, Crowther D, Sutcliffe SB, et al.: Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol 7 (11): 1630-6, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2809679" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2809679</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_12_2">Barrington SF, Kirkwood AA, Franceschetto A, et al.: PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study. Blood 127 (12): 1531-8, 2016. [<a href="https://pubmed.ncbi.nlm.nih.gov/26747247" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26747247</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_12_3">Urba WJ, Longo DL: Hodgkin's disease. N Engl J Med 326 (10): 678-87, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1736106" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1736106</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_12_4">Sombeck MD, Mendenhall NP, Kaude JV, et al.: Correlation of lymphangiography, computed tomography, and laparotomy in the staging of Hodgkin's disease. Int J Radiat Oncol Biol Phys 25 (3): 425-9, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8436520" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8436520</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_12_5">Mauch P, Larson D, Osteen R, et al.: Prognostic factors for positive surgical staging in patients with Hodgkin's disease. J Clin Oncol 8 (2): 257-65, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2299369" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2299369</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_12_6">Dietrich PY, Henry-Amar M, Cosset JM, et al.: Second primary cancers in patients continuously disease-free from Hodgkin's disease: a protective role for the spleen? Blood 84 (4): 1209-15, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8049435" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8049435</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_12_7">Adams HJ, Kwee TC, de Keizer B, et al.: Systematic review and meta-analysis on the diagnostic performance of FDG-PET/CT in detecting bone marrow involvement in newly diagnosed Hodgkin lymphoma: is bone marrow biopsy still necessary? Ann Oncol 25 (5): 921-7, 2014. [<a href="https://pubmed.ncbi.nlm.nih.gov/24351400" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24351400</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_12_8">Bradley AJ, Carrington BM, Lawrance JA, et al.: Assessment and significance of mediastinal bulk in Hodgkin's disease: comparison between computed tomography and chest radiography. J Clin Oncol 17 (8): 2493-8, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10561314" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10561314</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_12_9">Mauch P, Goodman R, Hellman S: The significance of mediastinal involvement in early stage Hodgkin's disease. Cancer 42 (3): 1039-45, 1978. [<a href="https://pubmed.ncbi.nlm.nih.gov/698907" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 698907</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_12_10">Carbone PP, Kaplan HS, Musshoff K, et al.: Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res 31 (11): 1860-1, 1971. [<a href="https://pubmed.ncbi.nlm.nih.gov/5121694" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 5121694</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_12_11">Hodgkin and non-Hodgkin lymphomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 607-11.</div></li><li><div class="bk_ref" id="CDR0000062675_rl_12_12">Jost LM, Stahel RA; ESMO Guidelines Task Force: ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of Hodgkin's disease. Ann Oncol 16 (Suppl 1): i54-5, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/15888755" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15888755</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_12_13">Hasenclever D, Diehl V: A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. N Engl J Med 339 (21): 1506-14, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9819449" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9819449</span></a>]</div></li></ol></div></div><div id="CDR0000062675__36"><h2 id="_CDR0000062675__36_">Treatment Option Overview for Adult HL</h2><p id="CDR0000062675__38">After initial clinical staging for Hodgkin lymphoma (HL), patients with early favorable disease or early unfavorable disease are treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy with or without involved-field or nodal radiation.</p><p id="CDR0000062675__998">Patients with advanced-stage disease are primarily treated with chemotherapy alone, although subsequent radiation therapy may be applied for initial bulky disease (≥10 cm mediastinal mass) or for residual adenopathy (>2.5 cm) with positive findings after a postchemotherapy positron emission tomography (PET) scan.[<a class="bk_pop" href="#CDR0000062675_rl_36_1">1</a>] Treatment regimen preferences and application, as well as relative risks, differ regionally.</p><p id="CDR0000062675__747">Patients with HL who are older than 60 years may have more treatment-related morbidity and mortality; maintaining the dose intensity of standard chemotherapy may be difficult.[<a class="bk_pop" href="#CDR0000062675_rl_36_2">2</a>,<a class="bk_pop" href="#CDR0000062675_rl_36_3">3</a>] Other therapies have been proposed for elderly patients, but no randomized trials have been conducted with these regimens.[<a class="bk_pop" href="#CDR0000062675_rl_36_4">4</a>] Twenty-seven previously untreated patients older than 60 years, judged by the investigator to be in poor condition and unable to undergo chemotherapy, received brentuximab. A 92% overall response rate and 73% complete remission rate were reported.[<a class="bk_pop" href="#CDR0000062675_rl_36_5">5</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>]</p><div id="CDR0000062675__883" class="table"><h3><span class="title">Table 3. Standard Treatment Options for Adult Hodgkin Lymphoma</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK66038.13/table/CDR0000062675__883/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062675__883_lrgtbl__"><table class="no_top_margin"><thead><tr><th colspan="1" rowspan="1" style="vertical-align:top;">Prognostic Group</th><th colspan="1" rowspan="1" style="vertical-align:top;">Standard Treatment Options</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Early favorable classic HL
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</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__922">Chemotherapy with or without radiation therapy</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Early unfavorable classic HL
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</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__924">Chemotherapy with or without radiation therapy</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Advanced classic HL
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</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__930">Chemotherapy</a></td></tr><tr><td colspan="1" rowspan="5" style="vertical-align:top;">Recurrent adult classic HL
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</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__1047">Brentuximab</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__1083">Chemotherapy with stem cell transplant</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__1066">Nivolumab or pembrolizumab </a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__933">Combination chemotherapy</a>
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</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__937">Radiation therapy</a></td></tr><tr><td colspan="1" rowspan="3" style="vertical-align:top;">NLPHL</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__1111">Radiation therapy</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__1114">Chemotherapy</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__1117">Rituximab</a></td></tr><tr><td colspan="1" rowspan="3" style="vertical-align:top;">HL during pregnancy</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__983">Watchful waiting</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__985">Radiation therapy</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__986">Chemotherapy</a></td></tr><tr><td colspan="2" rowspan="1" style="vertical-align:top;">HL = Hodgkin lymphoma; NLPHL = nodular lymphocyte-predominant Hodgkin lymphoma.</td></tr></tbody></table></div></div><div id="CDR0000062675__748"><h3>Chemotherapy</h3><p id="CDR0000062675__942">Table 4 describes the chemotherapy regimens used in the treatment of HL.</p><div id="CDR0000062675__1152" class="table"><h3><span class="title">Table 4. Chemotherapy Regimens Used to Treat Hodgkin Lymphoma</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK66038.13/table/CDR0000062675__1152/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062675__1152_lrgtbl__"><table class="no_top_margin"><thead><tr><th colspan="1" rowspan="1" style="vertical-align:top;">Combination Name</th><th colspan="1" rowspan="1" style="vertical-align:top;">Drugs Included</th><th colspan="1" rowspan="1" style="vertical-align:top;">Prognostic Group</th></tr></thead><tbody><tr><td colspan="1" rowspan="2" style="vertical-align:top;">ABVD</td><td colspan="1" rowspan="2" style="vertical-align:top;">Doxorubicin, bleomycin, vinblastine, and dacarbazine</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__362">Early favorable classic</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__373">Early unfavorable classic</a></td></tr><tr><td colspan="1" rowspan="2" style="vertical-align:top;">BEACOPP</td><td colspan="1" rowspan="2" style="vertical-align:top;">Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__373">Early unfavorable classic</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062675__402">Advanced classic</a></td></tr></tbody></table></div></div></div><div id="CDR0000062675__322"><h3>Radiation Therapy</h3><p id="CDR0000062675__323">Radiation therapy alone is almost never used to treat patients newly diagnosed with early favorable classic HL. In adult HL, the appropriate dose of radiation alone is 25 Gy to 30 Gy to
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clinically uninvolved sites and 35 Gy to 44 Gy to regions of initial
|
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nodal involvement.[<a class="bk_pop" href="#CDR0000062675_rl_36_6">6</a>-<a class="bk_pop" href="#CDR0000062675_rl_36_9">9</a>] Treatment is
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usually delivered to the neck, chest, and axilla (mantle field) and then to an
|
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abdominal field to treat para-aortic nodes and the spleen (splenic pedicle). In some patients, pelvic nodes are treated with
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a third field. The three fields constitute total nodal radiation therapy. In some
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cases, the pelvic and para-aortic nodes are treated in a single field called an
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inverted Y.[<a class="bk_pop" href="#CDR0000062675_rl_36_6">6</a>-<a class="bk_pop" href="#CDR0000062675_rl_36_9">9</a>] </p></div><div id="CDR0000062675_rl_36"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062675_rl_36_1">Engert A, Haverkamp H, Kobe C, et al.: Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet 379 (9828): 1791-9, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/22480758" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22480758</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_36_2">Böll B, Görgen H, Fuchs M, et al.: ABVD in older patients with early-stage Hodgkin lymphoma treated within the German Hodgkin Study Group HD10 and HD11 trials. J Clin Oncol 31 (12): 1522-9, 2013. [<a href="https://pubmed.ncbi.nlm.nih.gov/23509310" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23509310</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_36_3">Evens AM, Hong F: How can outcomes be improved for older patients with Hodgkin lymphoma? J Clin Oncol 31 (12): 1502-5, 2013. [<a href="https://pubmed.ncbi.nlm.nih.gov/23509323" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23509323</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_36_4">Kolstad A, Nome O, Delabie J, et al.: Standard CHOP-21 as first line therapy for elderly patients with Hodgkin's lymphoma. Leuk Lymphoma 48 (3): 570-6, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17454601" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17454601</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_36_5">Forero-Torres A, Holkova B, Goldschmidt J, et al.: Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older. Blood 126 (26): 2798-804, 2015. [<a href="/pmc/articles/PMC4692140/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4692140</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26377597" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26377597</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_36_6">Sears JD, Greven KM, Ferree CR, et al.: Definitive irradiation in the treatment of Hodgkin's disease. Analysis of outcome, prognostic factors, and long-term complications. Cancer 79 (1): 145-51, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/8988739" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8988739</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_36_7">Ng AK, Mauch PM: Radiation therapy in Hodgkin's lymphoma. Semin Hematol 36 (3): 290-302, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10462329" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10462329</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_36_8">Dühmke E, Franklin J, Pfreundschuh M, et al.: Low-dose radiation is sufficient for the noninvolved extended-field treatment in favorable early-stage Hodgkin's disease: long-term results of a randomized trial of radiotherapy alone. J Clin Oncol 19 (11): 2905-14, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11387364" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11387364</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_36_9">Mendenhall NP, Rodrigue LL, Moore-Higgs GJ, et al.: The optimal dose of radiation in Hodgkin's disease: an analysis of clinical and treatment factors affecting in-field disease control. Int J Radiat Oncol Biol Phys 44 (3): 551-61, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10348284" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10348284</span></a>]</div></li></ol></div></div><div id="CDR0000062675__362"><h2 id="_CDR0000062675__362_">Early Favorable Classic HL Treatment</h2><p id="CDR0000062675__364">Patients are designated as having early favorable classic Hodgkin lymphoma (HL) when they have clinical stage I or stage II disease and none of the following adverse prognostic factors:</p><ul id="CDR0000062675__365"><li class="half_rhythm"><div>B symptoms (unexplained fever ≥38°C, soaking night sweats, unexplained weight loss ≥10% within 6 months).</div></li><li class="half_rhythm"><div>Extranodal disease.</div></li><li class="half_rhythm"><div>Bulky disease (≥10 cm or >33% of the chest diameter on chest x-ray).</div></li><li class="half_rhythm"><div>Three or more sites of nodal involvement.</div></li><li class="half_rhythm"><div>Sedimentation rate of 50 mm/h or higher.</div></li></ul><div id="CDR0000062675__1143"><h3>Treatment Options for Early Favorable Classic HL</h3><p id="CDR0000062675__786">Treatment options for early favorable classic HL include the following:</p><ol id="CDR0000062675__921"><li class="half_rhythm"><div><a href="#CDR0000062675__922">Chemotherapy with or without radiation therapy</a>.</div></li></ol><div id="CDR0000062675__922"><h4>Chemotherapy with or without radiation therapy</h4><p id="CDR0000062675__923">Treatment options include the following:</p><ul id="CDR0000062675__788"><li class="half_rhythm"><div>ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for three to six cycles.[<a class="bk_pop" href="#CDR0000062675_rl_362_1">1</a>]</div></li><li class="half_rhythm"><div>ABVD for two to four cycles plus involved-field radiation therapy (IF-XRT) (20 Gy or 30 Gy).</div></li><li class="half_rhythm"><div>Radiation therapy alone in certain circumstances (such as for an elderly patient with absolute contraindications for using chemotherapy).[<a class="bk_pop" href="#CDR0000062675_rl_362_2">2</a>,<a class="bk_pop" href="#CDR0000062675_rl_362_3">3</a>]</div></li></ul><p id="CDR0000062675__366">Historically, radiation therapy alone was the primary treatment for patients with early favorable classic HL, often after confirmatory negative staging laparotomy.</p><p id="CDR0000062675__951">The late mortality from solid tumors (especially in the lung, breast, gastrointestinal tract, and connective tissue) and cardiovascular disease makes radiation therapy a less-attractive option for the best-risk patients, who have the highest probability of cure and long-term survival.[<a class="bk_pop" href="#CDR0000062675_rl_362_4">4</a>-<a class="bk_pop" href="#CDR0000062675_rl_362_8">8</a>] Clinical trials have focused on regimens with chemotherapy and IF-XRT or with chemotherapy alone.[<a class="bk_pop" href="#CDR0000062675_rl_362_1">1</a>]</p><p id="CDR0000062675__790">Evidence (chemotherapy and/or radiation therapy):</p><p id="CDR0000062675__1095">For patients with early favorable classic HL, the following four trials established ABVD alone for four cycles or ABVD for two cycles plus 20 Gy of IF-XRT.</p><ol id="CDR0000062675__791"><li class="half_rhythm"><div class="half_rhythm">A randomized, prospective trial from the National Cancer Institute of Canada involving 123 patients with early favorable classic HL compared ABVD for four to six cycles with subtotal nodal radiation.[<a class="bk_pop" href="#CDR0000062675_rl_362_9">9</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]<ul id="CDR0000062675__793"><li class="half_rhythm"><div>With a median follow-up of 11.3 years, no difference was observed in event-free survival (89% vs. 86%; <i>P</i> = .64) or in overall survival (OS) (98% vs. 98%; <i>P</i> = .95).</div></li></ul></div></li><li class="half_rhythm"><div class="half_rhythm">A randomized study from the Milan Cancer Institute of patients with clinical early-stage HL compared 4 months of ABVD followed by IF-XRT with 4 months of ABVD followed by extended-field radiation therapy (EF-XRT).[<a class="bk_pop" href="#CDR0000062675_rl_362_10">10</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335129/" class="def">Level of evidence: 1iiDii</a>]<ul id="CDR0000062675__864"><li class="half_rhythm"><div>The results showed similar OS and freedom from progression of disease with a 10-year median follow-up, but the study had inadequate statistical power to determine noninferiority of IF-XRT versus EF-XRT.</div></li></ul></div></li><li class="half_rhythm"><div class="half_rhythm">The German Hodgkin Study Group (GHSG) randomly assigned 1,190 patients with early favorable HL to receive one of the following:[<a class="bk_pop" href="#CDR0000062675_rl_362_11">11</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]<ul id="CDR0000062675__1148"><li class="half_rhythm"><div>Two cycles of ABVD plus 30 Gy of IF-XRT.</div></li><li class="half_rhythm"><div>Two cycles of ABVD plus 20 Gy of IF-XRT.</div></li><li class="half_rhythm"><div>Four cycles of ABVD plus 30 Gy of IF-XRT.</div></li><li class="half_rhythm"><div>Four cycles of ABVD plus 20 Gy of IF-XRT.
|
||
</div></li></ul></div><div class="half_rhythm">The following results were observed:<ul id="CDR0000062675__1097"><li class="half_rhythm"><div>With a 7.6-year median follow-up, no differences were observed in freedom from disease progression (97%) or OS (98%) for all four groups.</div></li></ul></div></li><li class="half_rhythm"><div class="half_rhythm">A follow-up study by the GHSG compared modified versions of ABVD with elimination of dacarbazine, bleomycin, or both in combination with 30 Gy of radiation therapy in 1,502 patients with early favorable HL.[<a class="bk_pop" href="#CDR0000062675_rl_362_12">12</a>] <ul id="CDR0000062675__1125"><li class="half_rhythm"><div>After 5 years, freedom from treatment failure was significantly worse when dacarbazine, bleomycin, or both were omitted. </div></li><li class="half_rhythm"><div>This trial suggests that ABVD remains the standard chemotherapy regimen.</div></li></ul></div></li></ol><p id="CDR0000062675__1000">Other trials have investigated the role of positron emission tomography (PET) scans for early favorable HL.</p><ol id="CDR0000062675__1126"><li class="half_rhythm"><div>Two prospective randomized trials of 1,739 patients with early-stage disease investigated the use of PET‒computed tomography (CT) scans to modify therapy.[<a class="bk_pop" href="#CDR0000062675_rl_362_13">13</a>,<a class="bk_pop" href="#CDR0000062675_rl_362_14">14</a>]<ul id="CDR0000062675__1127"><li class="half_rhythm"><div>Among patients with early favorable HL who had negative PET-CT scan results (Deauville 1 or 2) after two or three cycles of ABVD, radiation therapy could be omitted with no significant loss of progression-free survival or OS.[<a class="bk_pop" href="#CDR0000062675_rl_362_13">13</a>,<a class="bk_pop" href="#CDR0000062675_rl_362_14">14</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335131/" class="def">Level of evidence: 1iiDiii</a>]</div></li><li class="half_rhythm"><div>ABVD was given for three cycles (six doses) in one of the studies [<a class="bk_pop" href="#CDR0000062675_rl_362_14">14</a>] and for four cycles (eight doses) in the other study [<a class="bk_pop" href="#CDR0000062675_rl_362_13">13</a>] when applied without radiation therapy.</div></li><li class="half_rhythm"><div>Neither study randomly assigned therapy for positive results from an interim PET-CT scan (Deauville 3, 4, or 5) after two or three cycles of ABVD because this occurred in only 15% to 25% of the patients studied. One of the studies added an extra cycle of ABVD and IF-XRT to 30 Gy,[<a class="bk_pop" href="#CDR0000062675_rl_362_14">14</a>] while the other study switched to BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone)–escalated therapy for two cycles plus involved nodal radiation therapy to 30 Gy.[<a class="bk_pop" href="#CDR0000062675_rl_362_13">13</a>]</div></li></ul></div></li></ol><p id="CDR0000062675__1001"><b>Older patients with early favorable HL have also been studied.</b></p><ol id="CDR0000062675__1128"><li class="half_rhythm"><div>In 287 patients older than 60 years or with early favorable disease, a retrospective review of pulmonary toxicity in the HD10 and HD13 trials showed the following:[<a class="bk_pop" href="#CDR0000062675_rl_362_15">15</a>]<ul id="CDR0000062675__1129"><li class="half_rhythm"><div>Two cycles of ABVD plus IF-XRT (137 patients): 2% pulmonary toxicity.</div></li><li class="half_rhythm"><div>Two cycles of AVD (omitting bleomycin) plus IF-XRT (82 patients): 2% pulmonary toxicity.</div></li><li class="half_rhythm"><div>Four cycles of ABVD plus IF-XRT (68 patients): 10% pulmonary toxicity.</div></li></ul></div></li></ol><p id="CDR0000062675__1005"><b>For older patients (>60 y) with early favorable disease, when more than two cycles of ABVD are required, bleomycin may be omitted to avoid pulmonary toxicity.</b></p><p id="CDR0000062675__1006">To summarize:</p><ul id="CDR0000062675__1007"><li class="half_rhythm"><div>ABVD alone for three to four cycles is recommended for patients with early favorable classical HL when the interim PET-CT scan results are negative after two or three cycles of chemotherapy. These patients are also unlikely to ever relapse, so routine CT scans are not recommended in <a href="#CDR0000062675__970">follow-up</a>.</div></li><li class="half_rhythm"><div>With positive interim PET-CT scan results, extra cycles of ABVD and involved nodal radiation therapy are recommended.</div></li><li class="half_rhythm"><div>A combined modality approach with two cycles of ABVD and 20 Gy of IF-XRT can also be used for patients with early favorable classic HL. In this situation, a PET-CT scan to assess response after completion of therapy would suffice.</div></li></ul></div></div><div id="CDR0000062675__TrialSearch_362_sid_5"><h3>Current Clinical Trials</h3><p id="CDR0000062675__TrialSearch_362_22">Use our <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/advanced-search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062675_rl_362"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062675_rl_362_1">Canellos GP, Abramson JS, Fisher DC, et al.: Treatment of favorable, limited-stage Hodgkin's lymphoma with chemotherapy without consolidation by radiation therapy. J Clin Oncol 28 (9): 1611-5, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20159818" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20159818</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_362_2">Landgren O, Axdorph U, Fears TR, et al.: A population-based cohort study on early-stage Hodgkin lymphoma treated with radiotherapy alone: with special reference to older patients. Ann Oncol 17 (8): 1290-5, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16740597" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16740597</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_362_3">Backstrand KH, Ng AK, Takvorian RW, et al.: Results of a prospective trial of mantle irradiation alone for selected patients with early-stage Hodgkin's disease. J Clin Oncol 19 (3): 736-41, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11157025" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11157025</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_362_4">Dores GM, Metayer C, Curtis RE, et al.: Second malignant neoplasms among long-term survivors of Hodgkin's disease: a population-based evaluation over 25 years. J Clin Oncol 20 (16): 3484-94, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/12177110" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12177110</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_362_5">Reinders JG, Heijmen BJ, Olofsen-van Acht MJ, et al.: Ischemic heart disease after mantlefield irradiation for Hodgkin's disease in long-term follow-up. Radiother Oncol 51 (1): 35-42, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10386715" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10386715</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_362_6">Longo DL: Radiation therapy in Hodgkin disease: why risk a Pyrrhic victory? J Natl Cancer Inst 97 (19): 1394-5, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/16204683" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16204683</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_362_7">Swerdlow AJ, Higgins CD, Smith P, et al.: Myocardial infarction mortality risk after treatment for Hodgkin disease: a collaborative British cohort study. J Natl Cancer Inst 99 (3): 206-14, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17284715" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17284715</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_362_8">Engert A, Franklin J, Eich HT, et al.: Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial. J Clin Oncol 25 (23): 3495-502, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17606976" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17606976</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_362_9">Meyer RM, Gospodarowicz MK, Connors JM, et al.: ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med 366 (5): 399-408, 2012. [<a href="/pmc/articles/PMC3932020/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3932020</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22149921" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22149921</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_362_10">Bonadonna G, Bonfante V, Viviani S, et al.: ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin's disease: long-term results. J Clin Oncol 22 (14): 2835-41, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15199092" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15199092</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_362_11">Engert A, Plütschow A, Eich HT, et al.: Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med 363 (7): 640-52, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20818855" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20818855</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_362_12">Behringer K, Goergen H, Hitz F, et al.: Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet 385 (9976): 1418-27, 2015. [<a href="https://pubmed.ncbi.nlm.nih.gov/25539730" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25539730</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_362_13">Raemaekers JM, André MP, Federico M, et al.: Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol 32 (12): 1188-94, 2014. [<a href="https://pubmed.ncbi.nlm.nih.gov/24637998" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24637998</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_362_14">Radford J, Illidge T, Counsell N, et al.: Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. N Engl J Med 372 (17): 1598-607, 2015. [<a href="https://pubmed.ncbi.nlm.nih.gov/25901426" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25901426</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_362_15">Böll B, Goergen H, Behringer K, et al.: Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood 127 (18): 2189-92, 2016. [<a href="https://pubmed.ncbi.nlm.nih.gov/26834240" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26834240</span></a>]</div></li></ol></div></div><div id="CDR0000062675__373"><h2 id="_CDR0000062675__373_">Early Unfavorable Classic HL Treatment</h2><p id="CDR0000062675__375">Patients are designated as having early unfavorable classic Hodgkin lymphoma (HL) when they have clinical stage I or stage II disease and one or more of the following risk factors:</p><ul id="CDR0000062675__376"><li class="half_rhythm"><div>B symptoms (unexplained fever ≥38°C, soaking night sweats, unexplained weight loss ≥10% within 6 months). </div></li><li class="half_rhythm"><div>Extranodal disease.</div></li><li class="half_rhythm"><div>Bulky disease (≥10 cm or >33% of the chest diameter on chest x-ray).</div></li><li class="half_rhythm"><div>Three or more sites of nodal involvement.</div></li><li class="half_rhythm"><div>Sedimentation rate of 50 mm/h or higher.</div></li></ul><div id="CDR0000062675__1145"><h3>Standard Treatment Options for Early Unfavorable Classic HL</h3><p id="CDR0000062675__797">Treatment options for early unfavorable classic HL include the following:</p><ol id="CDR0000062675__898"><li class="half_rhythm"><div><a href="#CDR0000062675__924">Chemotherapy with or without radiation therapy</a>.</div></li></ol><div id="CDR0000062675__924"><h4>Chemotherapy with or without radiation therapy</h4><p id="CDR0000062675__925">Treatment options include the following:[<a class="bk_pop" href="#CDR0000062675_rl_373_1">1</a>,<a class="bk_pop" href="#CDR0000062675_rl_373_2">2</a>]</p><ul id="CDR0000062675__799"><li class="half_rhythm"><div>Four cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) plus involved-field radiation therapy (IF-XRT) (20 Gy–30 Gy).</div></li><li class="half_rhythm"><div>Six cycles of ABVD.[<a class="bk_pop" href="#CDR0000062675_rl_373_1">1</a>,<a class="bk_pop" href="#CDR0000062675_rl_373_2">2</a>]</div></li></ul><p id="CDR0000062675__800">Refer to <a class="figpopup" href="/books/NBK66038.13/table/CDR0000062675__1152/?report=objectonly" target="object" rid-figpopup="figCDR00000626751152" rid-ob="figobCDR00000626751152">Table 4</a> for a description of the chemotherapy regimens used to treat HL.</p><p id="CDR0000062675__801">Evidence (chemotherapy and radiation therapy):</p><ol id="CDR0000062675__802"><li class="half_rhythm"><div class="half_rhythm">A randomized, prospective trial from the National Cancer Institute of Canada (NCIC) involving 276 patients with early unfavorable HL compared ABVD for four to six cycles with ABVD for two cycles plus extended-field radiation therapy (EF-XRT).[<a class="bk_pop" href="#CDR0000062675_rl_373_1">1</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]<ul id="CDR0000062675__803"><li class="half_rhythm"><div>With a median follow-up of 11.3 years, the freedom from progression score favored combined-modality therapy (86% vs. 94%; <i>P</i> = .006), but the overall survival (OS) was better for ABVD alone (92% vs. 81%; <i>P</i> = .04).</div></li><li class="half_rhythm"><div>The trend toward a worse survival for the combined-modality arm was attributed to excess secondary malignancies and cardiovascular deaths. In this trial, the EF-XRT used higher doses and significantly larger exposure to body sites than are employed in current practice.</div></li><li class="half_rhythm"><div>This trial established that six cycles of ABVD can be applied alone and that long-term complications from radiation therapy can negate differences for progression-free survival (PFS).</div></li></ul></div></li><li class="half_rhythm"><div class="half_rhythm">In the HD11 trial, the German Hodgkin Study Group (GHSG) randomly assigned 1,395 patients with early unfavorable HL to receive one of the following:<ul id="CDR0000062675__1149"><li class="half_rhythm"><div>Four cycles of ABVD plus 30 Gy of IF-XRT.</div></li><li class="half_rhythm"><div>Four cycles of ABVD plus 20 Gy of IF-XRT.</div></li><li class="half_rhythm"><div>Four cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) plus 30 Gy of IF-XRT.</div></li><li class="half_rhythm"><div>Four cycles of BEACOPP plus 20 Gy of IF-XRT.</div></li></ul></div><div class="half_rhythm">The following results were observed:<ul id="CDR0000062675__472"><li class="half_rhythm"><div>With a 6.8-year median follow-up, no differences were observed in OS (93%–96%) for all four groups.[<a class="bk_pop" href="#CDR0000062675_rl_373_3">3</a>,<a class="bk_pop" href="#CDR0000062675_rl_373_4">4</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] </div></li><li class="half_rhythm"><div>In the study arms using 30 Gy of IF-XRT, there was no difference in freedom from treatment failure between BEACOPP and ABVD (<i>P</i> = .65), but a significant difference in favor of BEACOPP was seen for freedom from treatment failure when 20 Gy of IF-XRT was used (<i>P</i> = .02).[<a class="bk_pop" href="#CDR0000062675_rl_373_4">4</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000632558/" class="def">Level of evidence: 1iiD</a>]</div></li><li class="half_rhythm"><div>In this trial, four cycles of ABVD plus 30 Gy of IF-XRT established this regimen as the preferred approach.</div></li></ul></div></li><li class="half_rhythm"><div class="half_rhythm">In the HD14 trial, the GHSG randomly assigned 1,528 patients with early unfavorable HL to receive either four cycles of ABVD plus 30 Gy of IF-XRT or two cycles of escalated BEACOPP followed by two cycles of ABVD plus 30 Gy of IF-XRT.[<a class="bk_pop" href="#CDR0000062675_rl_373_5">5</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]<ul id="CDR0000062675__901"><li class="half_rhythm"><div>With a median follow-up of 43 months, no difference was observed in OS.</div></li><li class="half_rhythm"><div>In this trial, four cycles of ABVD plus 30 Gy of IF-XRT established this regimen as the preferred approach.</div></li></ul></div></li><li class="half_rhythm"><div class="half_rhythm">In the H9-U trial, the European Organisation for Research and Treatment of Cancer–Groupe d'Étude des Lymphomes de l'Adulte (EORTC/GELA) randomly assigned 808 patients with early unfavorable disease (including 40% with bulky disease) to receive one of the following:<ul id="CDR0000062675__1150"><li class="half_rhythm"><div>Six cycles of ABVD plus 36 Gy of IF-XRT.</div></li><li class="half_rhythm"><div>Four cycles of ABVD plus 36 Gy of IF-XRT.</div></li><li class="half_rhythm"><div>Four cycles of BEACOPP plus 36 Gy of IF-XRT.</div></li></ul></div><div class="half_rhythm">The following results were observed:<ul id="CDR0000062675__1010"><li class="half_rhythm"><div>With a median follow-up of 64 months, no differences were observed (event-free survival, 89%–92%; <i>P</i> = .38; or OS, 91%–96%; <i>P</i> = .89).</div></li><li class="half_rhythm"><div>Based on toxicities, four cycles of ABVD plus IF-XRT was established as the preferred regimen.</div></li></ul></div></li></ol><p id="CDR0000062675__810"><b>Could the radiation therapy be omitted to minimize late morbidity and mortality from secondary solid tumors and from cardiovascular disease?</b>[<a class="bk_pop" href="#CDR0000062675_rl_373_2">2</a>] </p><ul id="CDR0000062675__1139" class="simple-list"><li class="half_rhythm"><div>The NCIC study addressed this question in patients with early unfavorable HL; although four to six cycles of ABVD alone had improved OS compared with a combined-modality approach, the use of EF-XRT in the combined-modality arm is excessive by current standards, and late effects will be magnified with these larger fields.[<a class="bk_pop" href="#CDR0000062675_rl_373_1">1</a>] In addition, chemotherapy alone was 8% worse in freedom from disease progression compared with the combined-modality approach. An indirect comparison for using ABVD alone is that the 94% OS reported for patients with early unfavorable HL in the NCIC study [<a class="bk_pop" href="#CDR0000062675_rl_373_1">1</a>] at 11 years is equivalent to the survival reported at 11 years in the GHSG's <a href="https://clinicaltrials.gov/ct2/show/NCT02495922" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HD6</a> [<a href="https://clinicaltrials.gov/show/NCT00002561" title="Study NCT00002561" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT00002561</a>], <a href="https://clinicaltrials.gov/ct2/show/NCT00265018" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HD10</a> [<a href="https://clinicaltrials.gov/show/NCT01399931" title="Study NCT01399931" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT01399931</a>], and <a href="https://clinicaltrials.gov/ct2/show/NCT00264953" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">HD11</a> [NCT0264953] trials using combined-modality therapy.[<a class="bk_pop" href="#CDR0000062675_rl_373_6">6</a>] In addition, for the HD6 and HD10 trials, between the reports at 55 months and subsequently at 133 months, cardiovascular events doubled and solid tumor events tripled.[<a class="bk_pop" href="#CDR0000062675_rl_373_6">6</a>]</div></li></ul><p id="CDR0000062675__423">A Cochrane meta-analysis of 1,245 patients in five randomized clinical trials suggested improved survival for combined-modality therapy versus chemotherapy alone (hazard ratio, 0.40; 95% confidence interval, 0.27–0.61).[<a class="bk_pop" href="#CDR0000062675_rl_373_7">7</a>] However, the five randomized trials that were analyzed had inadequate follow-up to account for the late toxicities and increased mortality seen with radiation therapy after 10 years. </p><p id="CDR0000062675__1011"><b>Other trials have investigated the role of positron emission tomography‒computed tomography (PET-CT) scans for patients with early unfavorable HL.</b></p><ol id="CDR0000062675__1130"><li class="half_rhythm"><div>A randomized prospective trial of 1,196 patients with early unfavorable HL investigated the use of PET-CT scans to modify therapy after two cycles of therapy.[<a class="bk_pop" href="#CDR0000062675_rl_373_8">8</a>]<ol id="CDR0000062675__1151" class="lower-alpha"><li class="half_rhythm"><div>Among the 815 patients with negative PET-CT findings (Deauville 1, 2) after two cycles of ABVD, the patients randomly assigned to receive six cycles of ABVD had inferior PFS rates compared with patients who received four cycles of ABVD plus involved nodal radiation therapy (94.7% vs. 99.2%; <i>P</i> = .026), but no difference in OS.[<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335131/" class="def">Level of evidence: 1iiDiii</a>]</div></li><li class="half_rhythm"><div>The use of ABVD for six cycles is acceptable in the absence of radiation therapy for patients with early unfavorable classic HL who have negative PET-CT results after two cycles of ABVD, if one can accept a 5% rate of increased relapse, with no decrement in OS after salvage therapy.</div></li><li class="half_rhythm"><div>In a follow-up report from this trial, 381 patients with positive PET-CT results (Deauville 3, 4, 5) after two cycles of ABVD were randomly assigned to receive four cycles of ABVD plus 30 Gy of involved nodal radiation therapy versus two cycles of ABVD followed by two cycles of escalated BEACOPP plus 30 Gy of involved nodal radiation therapy.[<a class="bk_pop" href="#CDR0000062675_rl_373_9">9</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]<ul id="CDR0000062675__1132"><li class="half_rhythm"><div>5-year PFS rate was 91% in the BEACOPP arm compared with 77% in the ABVD arm (<i>P</i> = .002).</div></li><li class="half_rhythm"><div>5-year OS rate was 96% in the BEACOPP arm compared with 89% in the ABVD arm (<i>P</i> = .02).</div></li></ul></div></li></ol></div></li></ol><p id="CDR0000062675__1014">This trial supports adding escalated BEACOPP to ABVD for patients with early unfavorable classic HL who have positive PET-CT results after two cycles.</p><p id="CDR0000062675__1015">To summarize: </p><ul id="CDR0000062675__1123"><li class="half_rhythm"><div>Most of the trials support using four cycles of ABVD plus 30 Gy of IF-XRT or involved nodal radiation therapy. </div></li><li class="half_rhythm"><div>ABVD alone for six cycles is a reasonable alternative despite a 5% to 6% decrement in PFS because the long-term toxicities of adding radiation therapy will affect OS, which is the most important patient outcome. </div></li><li class="half_rhythm"><div>For patients with positive PET-CT results after two cycles of ABVD, escalated BEACOPP or clinical trials investigating brentuximab vedotin or the checkpoint inhibitors in this setting would be indicated.</div></li></ul><p id="CDR0000062675__389">Patients with bulky disease (≥10 cm) or massive mediastinal involvement were excluded from most of the aforementioned trials. On the basis of historical comparisons to chemotherapy or radiation therapy alone, these patients receive combined-modality therapy.[<a class="bk_pop" href="#CDR0000062675_rl_373_10">10</a>-<a class="bk_pop" href="#CDR0000062675_rl_373_12">12</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335158/" class="def">Level of evidence: 3iiiDiii</a>] A retrospective review published in a preliminary abstract reported on 194 patients with bulky disease who had PET-CT scans at the completion of chemotherapy; 112 of them had negative PET results (Deauville 1 or 2).[<a class="bk_pop" href="#CDR0000062675_rl_373_13">13</a>] The observed 86% OS at 5 years suggests that radiation therapy can be excluded for patients with massive mediastinal disease who have negative PET-CT scan results after six cycles of therapy.[<a class="bk_pop" href="#CDR0000062675_rl_373_13">13</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000593395/" class="def">Level of evidence: 3iiiD</a>]</p></div></div><div id="CDR0000062675__TrialSearch_373_sid_6"><h3>Current Clinical Trials</h3><p id="CDR0000062675__TrialSearch_373_22">Use our <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/advanced-search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062675_rl_373"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062675_rl_373_1">Meyer RM, Gospodarowicz MK, Connors JM, et al.: ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med 366 (5): 399-408, 2012. [<a href="/pmc/articles/PMC3932020/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3932020</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22149921" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22149921</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_373_2">Canellos GP, Abramson JS, Fisher DC, et al.: Treatment of favorable, limited-stage Hodgkin's lymphoma with chemotherapy without consolidation by radiation therapy. J Clin Oncol 28 (9): 1611-5, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20159818" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20159818</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_373_3">Diehl V, Brillant C, Engert A, et al.: Recent interim analysis of the HD11 trial of the GHSG: intensification of chemotherapy and reduction of radiation dose in early unfavorable stage Hodgkin's lymphoma. [Abstract] Blood 106 (11): A-816, 2005.</div></li><li><div class="bk_ref" id="CDR0000062675_rl_373_4">Eich HT, Diehl V, Görgen H, et al.: Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol 28 (27): 4199-206, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20713848" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20713848</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_373_5">von Tresckow B, Plütschow A, Fuchs M, et al.: Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German hodgkin study group HD14 trial. J Clin Oncol 30 (9): 907-13, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/22271480" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22271480</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_373_6">Meyer RM, Hoppe RT: Point/counterpoint: early-stage Hodgkin lymphoma and the role of radiation therapy. Blood 120 (23): 4488-95, 2012. [<a href="/pmc/articles/PMC3512228/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3512228</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22821764" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22821764</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_373_7">Herbst C, Rehan FA, Skoetz N, et al.: Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin lymphoma. Cochrane Database Syst Rev (2): CD007110, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/21328291" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21328291</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_373_8">Raemaekers JM, André MP, Federico M, et al.: Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol 32 (12): 1188-94, 2014. [<a href="https://pubmed.ncbi.nlm.nih.gov/24637998" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24637998</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_373_9">André MPE, Girinsky T, Federico M, et al.: Early Positron Emission Tomography Response-Adapted Treatment in Stage I and II Hodgkin Lymphoma: Final Results of the Randomized EORTC/LYSA/FIL H10 Trial. J Clin Oncol 35 (16): 1786-1794, 2017. [<a href="https://pubmed.ncbi.nlm.nih.gov/28291393" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28291393</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_373_10">Longo DL, Glatstein E, Duffey PL, et al.: Alternating MOPP and ABVD chemotherapy plus mantle-field radiation therapy in patients with massive mediastinal Hodgkin's disease. J Clin Oncol 15 (11): 3338-46, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9363863" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9363863</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_373_11">Horning SJ, Hoppe RT, Breslin S, et al.: Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: mature results of a prospective clinical trial. J Clin Oncol 20 (3): 630-7, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11821442" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11821442</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_373_12">Advani RH, Hong F, Fisher RI, et al.: Randomized Phase III Trial Comparing ABVD Plus Radiotherapy With the Stanford V Regimen in Patients With Stages I or II Locally Extensive, Bulky Mediastinal Hodgkin Lymphoma: A Subset Analysis of the North American Intergroup E2496 Trial. J Clin Oncol 33 (17): 1936-42, 2015. [<a href="/pmc/articles/PMC4451176/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4451176</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25897153" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25897153</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_373_13">Savage KJ: Advanced stage classical Hodgkin lymphoma patients with a negative PET-scan following treatment with ABVD have excellent outcomes without the need for consolidative radiotherapy regardless of disease bulk at presentation. [Abstract] Blood 126 (23): 579, 2015.</div></li></ol></div></div><div id="CDR0000062675__402"><h2 id="_CDR0000062675__402_">Advanced Classic HL Treatment</h2><p id="CDR0000062675__909">The following adverse prognostic factors for advanced classic Hodgkin lymphoma (HL) have been combined into the International Prognostic Score for advanced-stage Hodgkin lymphoma:[<a class="bk_pop" href="#CDR0000062675_rl_402_1">1</a>]</p><ul id="CDR0000062675__910"><li class="half_rhythm"><div> Albumin level lower than 4.0 g/L.</div></li><li class="half_rhythm"><div>Hemoglobin level lower than 10.5 g/L.</div></li><li class="half_rhythm"><div>Male sex.</div></li><li class="half_rhythm"><div>Age 45 years or older</div></li><li class="half_rhythm"><div>Stage IV disease.</div></li><li class="half_rhythm"><div>White blood cell (WBC) count of 15,000/mm<sup>3</sup> or higher.</div></li><li class="half_rhythm"><div>Absolute lymphocyte count lower than 600/mm<sup>3</sup> or a lymphocyte count higher than 8% of the total WBC count.</div></li></ul><div id="CDR0000062675__1082" class="table"><h3><span class="title">Table 5. Risk Factors and Survival Rates for Patients With Advanced Classic Hodgkin Lymphoma</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK66038.13/table/CDR0000062675__1082/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062675__1082_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">No. of Risk Factors</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">5-Year FFP (%)</th><th colspan="1" rowspan="1" style="text-align:center;vertical-align:top;">5-Year OS (%)</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">0</td><td colspan="1" rowspan="1" style="vertical-align:top;">88</td><td colspan="1" rowspan="1" style="vertical-align:top;">98</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">1</td><td colspan="1" rowspan="1" style="vertical-align:top;">84</td><td colspan="1" rowspan="1" style="vertical-align:top;">97</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">2</td><td colspan="1" rowspan="1" style="vertical-align:top;">80</td><td colspan="1" rowspan="1" style="vertical-align:top;">92</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">3</td><td colspan="1" rowspan="1" style="vertical-align:top;">74</td><td colspan="1" rowspan="1" style="vertical-align:top;">91</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">4</td><td colspan="1" rowspan="1" style="vertical-align:top;">67</td><td colspan="1" rowspan="1" style="vertical-align:top;">88</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">≥5</td><td colspan="1" rowspan="1" style="vertical-align:top;">62</td><td colspan="1" rowspan="1" style="vertical-align:top;">73</td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">FFP = freedom from progression; No. = number; OS = overall survival. </p></div></dd></dl></div></div></div><p id="CDR0000062675__1016">Even the highest-risk patients in this index have a 5-year freedom from progression rate above 60% and a 5-year OS rate above 70%.[<a class="bk_pop" href="#CDR0000062675_rl_402_1">1</a>]</p><div id="CDR0000062675__1146"><h3>Standard Treatment Options for Advanced Classic HL</h3><p id="CDR0000062675__820">Standard treatment options for advanced classic HL include the following:</p><ol id="CDR0000062675__911"><li class="half_rhythm"><div><a href="#CDR0000062675__930">Chemotherapy</a>.</div></li></ol><div id="CDR0000062675__930"><h4>Chemotherapy</h4><p id="CDR0000062675__931">The chemotherapy regimen ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) is administered for six cycles.</p><p id="CDR0000062675__823">Refer to <a class="figpopup" href="/books/NBK66038.13/table/CDR0000062675__1152/?report=objectonly" target="object" rid-figpopup="figCDR00000626751152" rid-ob="figobCDR00000626751152">Table 4 </a>for a description of the chemotherapy regimens used to treat HL.</p><p id="CDR0000062675__1133">Evidence (chemotherapy):</p><ol id="CDR0000062675__1140"><li class="half_rhythm"><div>In multiple prospective trials and a meta-analysis, ABVD therapy for 6 to 8 months remains the standard of care for patients with advanced HL, with equivalent overall survival (OS) when compared with other regimens (i.e., BEACOPP [bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone], escalated BEACOPP, Stanford V [doxorubicin, vinblastine, mechlorethamine, etoposide, vincristine, bleomycin, and prednisone], and MOPP-ABV [mechlorethamine, vincristine, procarbazine prednisone/doxorubicin, bleomycin, and vinblastine]).[<a class="bk_pop" href="#CDR0000062675_rl_402_2">2</a>-<a class="bk_pop" href="#CDR0000062675_rl_402_9">9</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]</div></li></ol><p id="CDR0000062675__1017"><b>Multiple studies have addressed the role of radiation therapy consolidation after induction chemotherapy for advanced-stage HL.</b></p><ol id="CDR0000062675__1134"><li class="half_rhythm"><div>Three prospective randomized trials did not show a benefit
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in OS from the addition of consolidative radiation therapy to
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chemotherapy for patients with advanced-stage disease.[<a class="bk_pop" href="#CDR0000062675_rl_402_10">10</a>-<a class="bk_pop" href="#CDR0000062675_rl_402_12">12</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]</div></li><li class="half_rhythm"><div>In a meta-analysis
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of 1,740 patients treated in 14 different trials, no improvement was observed in
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10-year OS for patients with advanced-stage HL who
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received combined-modality therapy versus chemotherapy alone.[<a class="bk_pop" href="#CDR0000062675_rl_402_13">13</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335150/" class="def">Level of
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evidence: 3iiiA</a>] </div></li><li class="half_rhythm"><div>No survival advantage is known for the use of radiation consolidation for patients with massive mediastinal disease and advanced-stage disease.[<a class="bk_pop" href="#CDR0000062675_rl_402_14">14</a>]</div></li><li class="half_rhythm"><div>The German Hodgkin Lymphoma Study Group HD15 trial showed that a negative positron emission tomography (PET) scan after induction therapy with BEACOPP (escalated or every 14 days) for advanced-stage HL was highly predictive for a good outcome, even with the omission of consolidative radiation therapy (negative predictive value for PET was 94% [95% confidence interval, 91%–97%]).[<a class="bk_pop" href="#CDR0000062675_rl_402_15">15</a>]</div></li></ol><p id="CDR0000062675__1135"><b>Other trials have investigated the role of PET scans for patients with advanced classic HL.</b></p><ol id="CDR0000062675__1136"><li class="half_rhythm"><div class="half_rhythm">A randomized, prospective trial of 1,214 patients with advanced-stage HL (Response adapted therapy for advanced Hodgkin lymphoma [RATHL study, <a href="https://clinicaltrials.gov/ct2/show/NCT00678327" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCT00678327</a>]) investigated the use of PET‒computed tomography (CT) scans after two cycles of ABVD to modify therapy.[<a class="bk_pop" href="#CDR0000062675_rl_402_16">16</a>] Patients with negative findings from a PET-CT scan (Deauville 1, 2, or 3) were randomly assigned to receive four more cycles of ABVD versus four cycles of AVD (omitting bleomycin).<ol id="CDR0000062675__1137" class="lower-alpha"><li class="half_rhythm"><div>With a median follow-up of 41 months for the 937 patients with negative PET-CT results, there was no difference in the 3-year OS (97.2%; 95% confidence interval [CI], 95.1–98.4 for ABVD vs. 97.6%; 95% CI, 95.6–98.7 for AVD).[<a class="bk_pop" href="#CDR0000062675_rl_402_16">16</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>]</div></li><li class="half_rhythm"><div>The absolute difference in the 3-year progression-free survival (PFS) (ABVD minus AVD) was 1.6% (95% CI, -3.2 to 5.3), which was just over the specified nonsuperiority margin. This means that there was a small advantage for continuing bleomycin on the basis of PFS.</div></li><li class="half_rhythm"><div>However, pulmonary toxicity was worse in the continued ABVD arm, with significantly more grade 3 or 4 respiratory events and worsened long-term diffusing capacity of the lung for carbon monoxide (DLCO) levels persisting beyond 1 year.</div></li><li class="half_rhythm"><div>This study concludes that bleomycin may be omitted after the second cycle of ABVD if findings from the PET-CT scan are negative (Deauville 1, 2, or 3).</div></li><li class="half_rhythm"><div>The patients with positive PET-CT scan results (Deauville 4 or 5) after two cycles of ABVD received BEACOPP.<ul id="CDR0000062675__1138"><li class="half_rhythm"><div>With a median follow-up of 41 months for the 172 patients with positive PET-CT results, the 3-year PFS rate was 67.5% and the OS rate was 87.8%</div></li><li class="half_rhythm"><div>This trial did not establish that switching to BEACOPP was superior to remaining on ABVD.</div></li></ul></div></li></ol></div></li><li class="half_rhythm"><div class="half_rhythm">A randomized prospective trial of 1,334 patients with previously untreated advanced-stage HL compared ABVD with a regimen substituting the chimeric antibody directed against CD30, brentuximab vedotin, for bleomycin (A+AVD).[<a class="bk_pop" href="#CDR0000062675_rl_402_17">17</a>] This trial utilized a "modified" PFS that was defined as progression, death, and any new therapy initiated for a poor response as defined by the investigators.<ul id="CDR0000062675__1141"><li class="half_rhythm"><div> With a median follow-up of 25 months, the 2-year modified PFS favored A+AVD versus ABVD with 82.1% versus 77.2% (hazard ratio [HR], 0.77; 95% CI, 0.60–0.98; <i>P</i> = .035).</div></li><li class="half_rhythm"><div> There was no difference in 2-year OS with A+AVD versus ABVD with 96.6% versus 94.9% (HR, 0.72; 95% CI, 0.44–1.17; <i>P</i> = .19).</div></li><li class="half_rhythm"><div> With A+AVD, there was significantly more febrile neutropenia (58% vs. 45%) and seven toxic deaths from febrile neutropenia, mandating growth factor support with granulocyte colony-stimulating factor (G-CSF) as an amendment during the trial. With A+AVD, there was significantly more grade 3 or 4 peripheral neuropathy (67% vs. 43%).</div></li><li class="half_rhythm"><div> With ABVD, there were 11 deaths from pulmonary toxicity.
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</div></li></ul></div><div class="half_rhythm">A+AVD does not represent a change in the standard of care (ABVD) because of the following: insufficient follow-up of long-term side effects and OS, no difference in OS at 2 years, a modest difference in modified PFS (4.9%), and mandated use of G-CSF. The avoidance of pulmonary toxicity with A+AVD is countered by the elimination of bleomycin for patients with negative PET scan results after the second treatment cycle. A+AVD can cost 50 times more than ABVD (in 2018).[<a class="bk_pop" href="#CDR0000062675_rl_402_17">17</a>]</div></li></ol><p id="CDR0000062675__1023">To summarize: </p><ul id="CDR0000062675__1124"><li class="half_rhythm"><div>For patients with advanced-stage HL, six cycles of ABVD is the standard approach. </div></li><li class="half_rhythm"><div>For patients with negative PET-CT scan results after the second cycle of ABVD, bleomycin may be omitted from the chemotherapy regimen with little loss of efficacy and improvement in tolerability.</div></li></ul></div></div><div id="CDR0000062675__TrialSearch_402_sid_7"><h3>Current Clinical Trials</h3><p id="CDR0000062675__TrialSearch_402_22">Use our <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/advanced-search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062675_rl_402"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062675_rl_402_1">Moccia AA, Donaldson J, Chhanabhai M, et al.: International Prognostic Score in advanced-stage Hodgkin's lymphoma: altered utility in the modern era. J Clin Oncol 30 (27): 3383-8, 2012. [<a href="https://pubmed.ncbi.nlm.nih.gov/22869887" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22869887</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_2">Canellos GP, Niedzwiecki D: Long-term follow-up of Hodgkin's disease trial. N Engl J Med 346 (18): 1417-8, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11986425" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11986425</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_3">Duggan DB, Petroni GR, Johnson JL, et al.: Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial. J Clin Oncol 21 (4): 607-14, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12586796" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12586796</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_4">Federico M, Luminari S, Iannitto E, et al.: ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin's lymphoma: results from the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol 27 (5): 805-11, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19124807" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19124807</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_5">Viviani S, Zinzani PL, Rambaldi A, et al.: ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med 365 (3): 203-12, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/21774708" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21774708</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_6">Bauer K, Skoetz N, Monsef I, et al.: Comparison of chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for patients with early unfavourable or advanced stage Hodgkin lymphoma. Cochrane Database Syst Rev (8): CD007941, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/21833963" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21833963</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_7">Chisesi T, Bellei M, Luminari S, et al.: Long-term follow-up analysis of HD9601 trial comparing ABVD versus Stanford V versus MOPP/EBV/CAD in patients with newly diagnosed advanced-stage Hodgkin's lymphoma: a study from the Intergruppo Italiano Linfomi. J Clin Oncol 29 (32): 4227-33, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/21990405" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21990405</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_8">Carde P, Karrasch M, Fortpied C, et al.: Eight Cycles of ABVD Versus Four Cycles of BEACOPPescalated Plus Four Cycles of BEACOPPbaseline in Stage III to IV, International Prognostic Score ≥ 3, High-Risk Hodgkin Lymphoma: First Results of the Phase III EORTC 20012 Intergroup Trial. J Clin Oncol 34 (17): 2028-36, 2016. [<a href="https://pubmed.ncbi.nlm.nih.gov/27114593" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27114593</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_9">Mounier N, Brice P, Bologna S, et al.: ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥ 4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol 25 (8): 1622-8, 2014. [<a href="https://pubmed.ncbi.nlm.nih.gov/24827123" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24827123</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_10">Fabian CJ, Mansfield CM, Dahlberg S, et al.: Low-dose involved field radiation after chemotherapy in advanced Hodgkin disease. A Southwest Oncology Group randomized study. Ann Intern Med 120 (11): 903-12, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/8172436" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8172436</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_11">Aleman BM, Raemaekers JM, Tirelli U, et al.: Involved-field radiotherapy for advanced Hodgkin's lymphoma. N Engl J Med 348 (24): 2396-406, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12802025" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12802025</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_12">Fermé C, Mounier N, Casasnovas O, et al.: Long-term results and competing risk analysis of the H89 trial in patients with advanced-stage Hodgkin lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte (GELA). Blood 107 (12): 4636-42, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16478882" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16478882</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_13">Loeffler M, Brosteanu O, Hasenclever D, et al.: Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin's disease. International Database on Hodgkin's Disease Overview Study Group. J Clin Oncol 16 (3): 818-29, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9508162" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9508162</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_14">Brice P, Colin P, Berger F, et al.: Advanced Hodgkin disease with large mediastinal involvement can be treated with eight cycles of chemotherapy alone after a major response to six cycles of chemotherapy: a study of 82 patients from the Groupes d'Etudes des Lymphomes de l'Adulte H89 trial. Cancer 92 (3): 453-9, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11505388" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11505388</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_15">Kobe C, Dietlein M, Franklin J, et al.: Positron emission tomography has a high negative predictive value for progression or early relapse for patients with residual disease after first-line chemotherapy in advanced-stage Hodgkin lymphoma. Blood 112 (10): 3989-94, 2008. [<a href="/pmc/articles/PMC2581984/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2581984</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18757777" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18757777</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_16">Johnson P, Federico M, Kirkwood A, et al.: Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma. N Engl J Med 374 (25): 2419-29, 2016. [<a href="/pmc/articles/PMC4961236/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4961236</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27332902" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27332902</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_402_17">Connors JM, Jurczak W, Straus DJ, et al.: Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med 378 (4): 331-344, 2018. [<a href="/pmc/articles/PMC5819601/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5819601</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29224502" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29224502</span></a>]</div></li></ol></div></div><div id="CDR0000062675__174"><h2 id="_CDR0000062675__174_">Recurrent Adult Classic HL Treatment</h2><p id="CDR0000062675__1043">At least half of all patients with recurrent Hodgkin lymphoma (HL) can achieve long-term disease-free survival (or even cure) using conventional chemotherapeutic agents followed by stem cell/bone marrow transplantation consolidation.[<a class="bk_pop" href="#CDR0000062675_rl_174_1">1</a>] In this regard, the disease follows a <i>75%</i><i> rule</i>: 75% of patients attain a clinical complete remission with salvage therapy reinduction, and then 75% of patients who undergo autologous stem cell transplantation (SCT) are free of disease at 4 years. Poor prognostic factors include the following:[<a class="bk_pop" href="#CDR0000062675_rl_174_2">2</a>-<a class="bk_pop" href="#CDR0000062675_rl_174_4">4</a>]</p><ul id="CDR0000062675__1044"><li class="half_rhythm"><div>Primary refractory disease (worst prognosis).</div></li><li class="half_rhythm"><div>Relapse less than 12 months after initial therapy.</div></li><li class="half_rhythm"><div>Inability to attain a clinical complete remission after reinduction (positron emission tomography‒computed tomography [PET-CT] scan results are positive with Deauville 4, 5).</div></li><li class="half_rhythm"><div>
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<a href="#CDR0000062675__966">B symptoms</a> at relapse.</div></li><li class="half_rhythm"><div>Extranodal disease at relapse.</div></li><li class="half_rhythm"><div>More than two previous salvage regimens received.</div></li></ul><div id="CDR0000062675__1147"><h3>Standard Treatment Options for Recurrent Adult Classic HL</h3><p id="CDR0000062675__1045">Standard treatment options for recurrent adult classic HL:</p><ol id="CDR0000062675__1046"><li class="half_rhythm"><div><a href="#CDR0000062675__1047">Brentuximab</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000062675__1083">Chemotherapy with stem cell transplant</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000062675__1066">Nivolumab or pembrolizumab</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000062675__933">Combination chemotherapy</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000062675__937">Radiation therapy</a>.</div></li></ol><div id="CDR0000062675__1047"><h4>Brentuximab</h4><p id="CDR0000062675__1048">Brentuximab vedotin is a chimeric antibody directed against CD30, which is linked to the microtubule-disrupting agent monomethyl auristatin E.[<a class="bk_pop" href="#CDR0000062675_rl_174_5">5</a>-<a class="bk_pop" href="#CDR0000062675_rl_174_7">7</a>] CD30 is a target for therapy because it is expressed on malignant Reed-Sternberg cells of HL, but has limited expression on normal cells. Brentuximab is well tolerated by patients and can be used to achieve a clinical complete response before autologous or allogeneic SCT.</p><p id="CDR0000062675__1049">Evidence (brentuximab):</p><ol id="CDR0000062675__1050"><li class="half_rhythm"><div>In several trials reported between 2010 and 2012, the following results were observed:<ul id="CDR0000062675__1051"><li class="half_rhythm"><div>For relapsing patients, response rates around 75% were seen, with complete remissions around 50% and median progression-free survival (PFS) of 4 to 8 months.[<a class="bk_pop" href="#CDR0000062675_rl_174_5">5</a>-<a class="bk_pop" href="#CDR0000062675_rl_174_8">8</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>] </div></li></ul></div></li><li class="half_rhythm"><div>Twenty-seven previously untreated patients older than 60 years, judged by the investigator to be in poor condition and unable to undergo chemotherapy, received brentuximab.[<a class="bk_pop" href="#CDR0000062675_rl_174_9">9</a>]<ul id="CDR0000062675__1052"><li class="half_rhythm"><div>A 92% overall response rate and 73% complete remission rate were reported.[<a class="bk_pop" href="#CDR0000062675_rl_174_9">9</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>]</div></li></ul></div></li><li class="half_rhythm"><div>Successful treatment with brentuximab for relapsed patients was reported, with a response rate of 60%.[<a class="bk_pop" href="#CDR0000062675_rl_174_10">10</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>]</div></li><li class="half_rhythm"><div>For 329 patients at high risk of residual HL after SCT, the double-blind <a href="https://clinicaltrials.gov/ct2/show/NCT01100502" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">AETHERA</a> trial [<a href="https://clinicaltrials.gov/show/NCT01100502" title="Study NCT01100502" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT01100502</a>] evaluated brentuximab vedotin versus placebo.<ul id="CDR0000062675__1053"><li class="half_rhythm"><div>The median PFS of 42.9 months for the brentuximab group was better than the 24.1 months for the control group (hazard ratio [HR], 0.57; 95% confidence interval, 0.40–0.81; <i>P</i> = .0013).[<a class="bk_pop" href="#CDR0000062675_rl_174_11">11</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335124/" class="def">Level of evidence: 1iDiii</a>]</div></li><li class="half_rhythm"><div>The 16-month treatment duration after transplantation was not achieved by most patients because they developed progressive peripheral neuropathy, which was partially reversible after discontinuation of brentuximab.</div></li><li class="half_rhythm"><div>It is unclear whether results of this trial are applicable when brentuximab is employed before transplantation, such as during reinduction after relapse or during initial therapy (presently under clinical evaluation).</div></li></ul></div></li></ol></div><div id="CDR0000062675__1083"><h4>Chemotherapy with stem cell transplant</h4><p id="CDR0000062675__1084">Patients who relapse after initial
|
||
combination chemotherapy can undergo reinduction with the same or another
|
||
chemotherapy regimen followed by high-dose chemotherapy and autologous bone
|
||
marrow or peripheral stem cell or allogeneic bone marrow rescue.[<a class="bk_pop" href="#CDR0000062675_rl_174_1">1</a>,<a class="bk_pop" href="#CDR0000062675_rl_174_12">12</a>-<a class="bk_pop" href="#CDR0000062675_rl_174_15">15</a>] This
|
||
therapy has resulted in 3- to 4-year disease-free survival (DFS) rates of up to 50%. Patients who are responsive to reinduction therapy may have a better
|
||
prognosis after subsequent autologous SCT; in one analysis, the 3-year event-free survival (EFS) rate was 80% with negative PET-CT scan results and 29% with positive PET-CT scan results.[<a class="bk_pop" href="#CDR0000062675_rl_174_16">16</a>]</p><p id="CDR0000062675__1085">Patients who do not respond to induction chemotherapy (about 20%‒25% of all presenting patients) have survival rates lower than 10% at 8 years.[<a class="bk_pop" href="#CDR0000062675_rl_174_3">3</a>] For these patients, high-dose chemotherapy and autologous bone marrow or peripheral stem cell or allogeneic bone marrow rescue [<a class="bk_pop" href="#CDR0000062675_rl_174_14">14</a>,<a class="bk_pop" href="#CDR0000062675_rl_174_15">15</a>,<a class="bk_pop" href="#CDR0000062675_rl_174_17">17</a>-<a class="bk_pop" href="#CDR0000062675_rl_174_23">23</a>] have resulted in 5-year DFS rates of around 25% to 30%, but selection bias clearly influences these numbers.[<a class="bk_pop" href="#CDR0000062675_rl_174_12">12</a>-<a class="bk_pop" href="#CDR0000062675_rl_174_15">15</a>,<a class="bk_pop" href="#CDR0000062675_rl_174_22">22</a>]</p><p id="CDR0000062675__1086">In a retrospective review of 105 patients, those older than 60 years fared better with a combination of chemotherapy and salvage radiation therapy than with the use of intensified transplant consolidation.[<a class="bk_pop" href="#CDR0000062675_rl_174_24">24</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>]</p><p id="CDR0000062675__1087">The use of HLA-matched sibling marrow (allogeneic transplantation) results
|
||
in lower relapse rates, but the benefit may be offset by increased toxic
|
||
effects.[<a class="bk_pop" href="#CDR0000062675_rl_174_14">14</a>,<a class="bk_pop" href="#CDR0000062675_rl_174_25">25</a>,<a class="bk_pop" href="#CDR0000062675_rl_174_26">26</a>] Reduced-intensity conditioning for allogeneic SCT is also under clinical evaluation.[<a class="bk_pop" href="#CDR0000062675_rl_174_27">27</a>-<a class="bk_pop" href="#CDR0000062675_rl_174_31">31</a>]</p><p id="CDR0000062675__1088">Evidence (chemotherapy with SCT):</p><ol id="CDR0000062675__1089"><li class="half_rhythm"><div>A randomized trial compared aggressive conventional chemotherapy versus high-dose chemotherapy with autologous hematopoietic SCT for relapsed chemosensitive HL.[<a class="bk_pop" href="#CDR0000062675_rl_174_32">32</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335129/" class="def">Level of evidence: 1iiDii</a>]<ul id="CDR0000062675__1090"><li class="half_rhythm"><div>This trial showed improvement in freedom from treatment failure at 3 years for the transplantation arm (55%) versus the chemotherapy-alone arm (34%).[<a class="bk_pop" href="#CDR0000062675_rl_174_32">32</a>]</div></li><li class="half_rhythm"><div>No difference was observed in overall survival (OS).</div></li></ul></div></li><li class="half_rhythm"><div>A Cochrane meta-analysis concluded that autologous SCT after reinduction chemotherapy improves relapse-free survival by 20% to 30% over chemotherapy alone, but without an OS benefit.[<a class="bk_pop" href="#CDR0000062675_rl_174_33">33</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335129/" class="def">Level of evidence: 1iiDii</a>]</div></li><li class="half_rhythm"><div>In two retrospective reviews of patients who
|
||
underwent autologous bone marrow transplantation (ABMT) for relapsed or refractory disease, a comparison was made between
|
||
those who received involved-field radiation therapy (IF-XRT) for residual masses after
|
||
high-dose therapy and those who received no further treatment.[<a class="bk_pop" href="#CDR0000062675_rl_174_34">34</a>,<a class="bk_pop" href="#CDR0000062675_rl_174_35">35</a>]<ul id="CDR0000062675__1091"><li class="half_rhythm"><div>Those who received
|
||
IF-XRT had improved PFS.</div></li><li class="half_rhythm"><div>Normalization of fluorine F 18-fludeoxyglucose PET-CT scans after reinduction therapy predicted a much better outcome after SCT, with an EFS rate of 80% versus 29% in one phase II trial.[<a class="bk_pop" href="#CDR0000062675_rl_174_16">16</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335153/" class="def">Level of evidence: 3iiiDi</a>]</div></li></ul></div></li></ol><p id="CDR0000062675__1092">After completion of autologous SCT for recurrent HL, 329 patients were randomly assigned to receive brentuximab vedotin or placebo in a double-blind trial (AETHERA [<a href="https://clinicaltrials.gov/show/NCT01100502" title="Study NCT01100502" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT01100502</a>]).</p><ul id="CDR0000062675__1093"><li class="half_rhythm"><div>The median PFS of 42.9 months for the brentuximab group was significantly better than the 24.1 months for the control group (HR, 0.57; 95% confidence interval [CI], 0.40–0.81, <i>P</i> = .0013).[<a class="bk_pop" href="#CDR0000062675_rl_174_11">11</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335124/" class="def">Level of evidence: 1iDiii</a>]</div></li><li class="half_rhythm"><div>The 16-month treatment duration after transplantation was not achieved by most patients because they developed progressive peripheral neuropathy, which was partially reversible after discontinuation of brentuximab.</div></li><li class="half_rhythm"><div>It is unclear whether the results of this trial are applicable when brentuximab is employed before transplantation, such as during reinduction after relapse or during initial therapy (presently under clinical evaluation).</div></li></ul><p id="CDR0000062675__1094">A phase II trial reported a response rate higher than 50% for bendamustine in relapsing ABMT patients.[<a class="bk_pop" href="#CDR0000062675_rl_174_36">36</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>] For patients with recurrent disease after ABMT, weekly
|
||
vinblastine therapy has provided palliation with minimal toxic
|
||
effects.[<a class="bk_pop" href="#CDR0000062675_rl_174_37">37</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>]</p></div><div id="CDR0000062675__1066"><h4>Nivolumab or pembrolizumab</h4><p id="CDR0000062675__1067">The anti-PD1 monoclonal antibodies nivolumab and pembrolizumab are immune checkpoint inhibitors.</p><p id="CDR0000062675__1068">Evidence (nivolumab):</p><ol id="CDR0000062675__1069"><li class="half_rhythm"><div>Studies of relapsed HL patients treated with nivolumab reported the following:[<a class="bk_pop" href="#CDR0000062675_rl_174_38">38</a>-<a class="bk_pop" href="#CDR0000062675_rl_174_40">40</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>] <ul id="CDR0000062675__1070"><li class="half_rhythm"><div>An overall response rate of 65% to 87% and a complete response rate of 16% to 28%, with durations usually exceeding 1 year for heavily pretreated, relapsed patients.</div></li><li class="half_rhythm"><div>Nivolumab is well tolerated by patients and can be used to achieve a clinical complete remission before autologous or allogeneic SCT.</div></li><li class="half_rhythm"><div>Nivolumab is approved by the U.S. Food and Drug Administration (FDA) for use after both relapse from SCT and previous exposure to brentuximab. Nivolumab is also approved if the patient has received three different previous treatments, including SCT.</div></li></ul></div></li></ol><p id="CDR0000062675__1071">Evidence: (pembrolizumab):</p><ol id="CDR0000062675__1072"><li class="half_rhythm"><div>Studies of relapsed HL patients treated with pembrolizumab reported the following:[<a class="bk_pop" href="#CDR0000062675_rl_174_41">41</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>]<ul id="CDR0000062675__1073"><li class="half_rhythm"><div>An overall response rate of 64% to 74%, with a complete response rate of 22.4% (95% CI, 6.9%–28.6%).</div></li><li class="half_rhythm"><div>Pembrolizumab is well tolerated by patients and can be used to achieve a clinical complete remission before autologous or allogeneic SCT.</div></li><li class="half_rhythm"><div>Pembrolizumab is FDA approved for use in cases of refractory disease or relapse after three or more lines of therapy.</div></li></ul></div></li></ol></div><div id="CDR0000062675__933"><h4>Combination chemotherapy</h4><p id="CDR0000062675__834">For patients who experience a relapse after initial
|
||
combination chemotherapy, prognosis is determined more by the duration of the
|
||
first remission than by the specific induction or salvage combination
|
||
chemotherapy regimen. Patients whose initial remission after chemotherapy was
|
||
longer than 1 year (late relapse) have long-term survival rates of 22% to 71% with salvage
|
||
chemotherapy.[<a class="bk_pop" href="#CDR0000062675_rl_174_2">2</a>-<a class="bk_pop" href="#CDR0000062675_rl_174_4">4</a>,<a class="bk_pop" href="#CDR0000062675_rl_174_42">42</a>-<a class="bk_pop" href="#CDR0000062675_rl_174_44">44</a>] Patients whose initial remission after
|
||
chemotherapy was shorter than 1 year (early relapse) do much worse and have
|
||
long-term survival rates of 11% to 46%.[<a class="bk_pop" href="#CDR0000062675_rl_174_2">2</a>,<a class="bk_pop" href="#CDR0000062675_rl_174_3">3</a>,<a class="bk_pop" href="#CDR0000062675_rl_174_45">45</a>]</p><p id="CDR0000062675__1074">In a retrospective review of 105 patients, those older than 60 years fared better with a combination of chemotherapy and salvage radiation therapy than with the use of intensified transplant consolidation.[<a class="bk_pop" href="#CDR0000062675_rl_174_24">24</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>]</p><p id="CDR0000062675__1075">It is rare to see a patient who received only radiation therapy for initial treatment, but patients who experience a relapse after initial wide-field, high-dose radiation
|
||
therapy have a good prognosis. Combination chemotherapy results in 10-year
|
||
DFS rates of 57% to 81% and OS rates of 57% to 89%.[<a class="bk_pop" href="#CDR0000062675_rl_174_2">2</a>,<a class="bk_pop" href="#CDR0000062675_rl_174_46">46</a>-<a class="bk_pop" href="#CDR0000062675_rl_174_48">48</a>]</p></div><div id="CDR0000062675__937"><h4>Radiation therapy</h4><p id="CDR0000062675__177">For the small subgroup of patients with only limited nodal recurrence following
|
||
initial chemotherapy, radiation therapy with or without additional chemotherapy
|
||
may provide long-term survival for about 50% of these highly selected patients.[<a class="bk_pop" href="#CDR0000062675_rl_174_49">49</a>,<a class="bk_pop" href="#CDR0000062675_rl_174_50">50</a>]</p></div><div id="CDR0000062675__1076"><h4>Summary for sequencing therapies for recurrent classic HL</h4><p id="CDR0000062675__1078">Transplant eligible:</p><ul id="CDR0000062675__1079"><li class="half_rhythm"><div>Start with brentuximab for two to four cycles. If clinical complete remission, proceed to autologous SCT.</div></li><li class="half_rhythm"><div>If partial response to or stable disease with brentuximab, proceed to chemotherapy with ICE (ifosfamide, carboplatin, etoposide) or GVD (gemcitabine, vinorelbine, liposomal doxorubicin). If clinical complete remission, proceed to autologous SCT.</div></li><li class="half_rhythm"><div>If partial response to or stable disease with chemotherapy, proceed to pembrolizumab (or nivolumab).</div></li><li class="half_rhythm"><div>Consider allogeneic SCT for primary refractory disease with partial response or complete remission on salvage therapy.</div></li></ul><p id="CDR0000062675__1080">Transplant ineligible:</p><ul id="CDR0000062675__1081"><li class="half_rhythm"><div>Start with brentuximab for two to four cycles. If clinical complete remission, continue until neuropathy forces discontinuation.</div></li><li class="half_rhythm"><div>If partial response or stable disease on brentuximab, use pembrolizumab or nivolumab and use for at least 1 year (studies are under way to define duration of therapy).</div></li><li class="half_rhythm"><div>Proceed to chemotherapy options for further palliation.</div></li></ul></div></div><div id="CDR0000062675__TrialSearch_174_sid_8"><h3>Current Clinical Trials</h3><p id="CDR0000062675__TrialSearch_174_22">Use our <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/advanced-search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062675_rl_174"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062675_rl_174_1">Holmberg L, Maloney DG: The role of autologous and allogeneic hematopoietic stem cell transplantation for Hodgkin lymphoma. J Natl Compr Canc Netw 9 (9): 1060-71, 2011. [<a href="/pmc/articles/PMC3207964/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3207964</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21917627" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21917627</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_2">Josting A, Franklin J, May M, et al.: New prognostic score based on treatment outcome of patients with relapsed Hodgkin's lymphoma registered in the database of the German Hodgkin's lymphoma study group. J Clin Oncol 20 (1): 221-30, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11773173" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11773173</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_3">Bonfante V, Santoro A, Viviani S, et al.: Outcome of patients with Hodgkin's disease failing after primary MOPP-ABVD. J Clin Oncol 15 (2): 528-34, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9053474" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9053474</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_4">Garcia-Carbonero R, Paz-Ares L, Arcediano A, et al.: Favorable prognosis after late relapse of Hodgkin's disease. Cancer 83 (3): 560-5, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9690550" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9690550</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_5">Gopal AK, Ramchandren R, O'Connor OA, et al.: Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation. Blood 120 (3): 560-8, 2012. [<a href="/pmc/articles/PMC3731651/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3731651</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22510871" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22510871</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_6">Younes A, Bartlett NL, Leonard JP, et al.: Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med 363 (19): 1812-21, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/21047225" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21047225</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_7">Younes A, Gopal AK, Smith SE, et al.: Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol 30 (18): 2183-9, 2012. [<a href="/pmc/articles/PMC3646316/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3646316</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22454421" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22454421</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_8">Chen R, Palmer JM, Thomas SH, et al.: Brentuximab vedotin enables successful reduced-intensity allogeneic hematopoietic cell transplantation in patients with relapsed or refractory Hodgkin lymphoma. Blood 119 (26): 6379-81, 2012. [<a href="/pmc/articles/PMC3383201/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3383201</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22611160" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22611160</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_9">Forero-Torres A, Holkova B, Goldschmidt J, et al.: Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older. Blood 126 (26): 2798-804, 2015. [<a href="/pmc/articles/PMC4692140/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4692140</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26377597" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26377597</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_10">Bartlett NL, Chen R, Fanale MA, et al.: Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies. J Hematol Oncol 7: 24, 2014. [<a href="/pmc/articles/PMC3994656/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3994656</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24642247" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24642247</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_11">Moskowitz CH, Nademanee A, Masszi T, et al.: Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 385 (9980): 1853-62, 2015. [<a href="https://pubmed.ncbi.nlm.nih.gov/25796459" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25796459</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_12">Nademanee A, O'Donnell MR, Snyder DS, et al.: High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodgkin's disease: results in 85 patients with analysis of prognostic factors. Blood 85 (5): 1381-90, 1995. 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Int J Radiat Oncol Biol Phys 36 (1): 3-12, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8823253" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8823253</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_36">Moskowitz AJ, Hamlin PA Jr, Perales MA, et al.: Phase II study of bendamustine in relapsed and refractory Hodgkin lymphoma. J Clin Oncol 31 (4): 456-60, 2013. [<a href="/pmc/articles/PMC3862960/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3862960</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23248254" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23248254</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_37">Little R, Wittes RE, Longo DL, et al.: Vinblastine for recurrent Hodgkin's disease following autologous bone marrow transplant. J Clin Oncol 16 (2): 584-8, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9469345" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9469345</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_38">Ansell SM, Lesokhin AM, Borrello I, et al.: PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med 372 (4): 311-9, 2015. [<a href="/pmc/articles/PMC4348009/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4348009</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25482239" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25482239</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_39">Younes A, Santoro A, Shipp M, et al.: Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol 17 (9): 1283-94, 2016. [<a href="/pmc/articles/PMC5541855/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5541855</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27451390" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27451390</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_40">Armand P, Shipp MA, Ribrag V, et al.: Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. J Clin Oncol 34 (31): 3733-3739, 2016. [<a href="/pmc/articles/PMC5791838/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5791838</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27354476" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27354476</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_41">Chen R, Zinzani PL, Fanale MA, et al.: Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J Clin Oncol 35 (19): 2125-2132, 2017. 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[<a href="https://pubmed.ncbi.nlm.nih.gov/7685241" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7685241</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_174_50">Josting A, Nogová L, Franklin J, et al.: Salvage radiotherapy in patients with relapsed and refractory Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Lymphoma Study Group. J Clin Oncol 23 (7): 1522-9, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/15632410" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15632410</span></a>]</div></li></ol></div></div><div id="CDR0000062675__1104"><h2 id="_CDR0000062675__1104_">Nodular Lymphocyte–Predominant HL (NLPHL) Treatment</h2><p id="CDR0000062675__1105">NLPHL (CD15-, CD20+, CD30-) has been distinguished from lymphocyte-rich classic HL (CD15+, CD20-, CD30+) on the basis of these immunophenotypic differences.[<a class="bk_pop" href="#CDR0000062675_rl_1104_1">1</a>,<a class="bk_pop" href="#CDR0000062675_rl_1104_2">2</a>] The largest retrospective report of 426 cases showed no significant difference in clinical response or outcome to standard therapies for these two subgroups when patients present with early-stage disease (stage I or II).[<a class="bk_pop" href="#CDR0000062675_rl_1104_3">3</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335150/" class="def">Level of evidence: 3iiiA</a>] </p><p id="CDR0000062675__1106">Patients with NLPHL have earlier-stage disease, longer survival, and fewer treatment failures than do those with classic HL.[<a class="bk_pop" href="#CDR0000062675_rl_1104_4">4</a>,<a class="bk_pop" href="#CDR0000062675_rl_1104_5">5</a>]</p><p id="CDR0000062675__1107">NLPHL is usually diagnosed in asymptomatic younger patients with cervical or inguinal lymph nodes but usually without mediastinal involvement.</p><div id="CDR0000062675__1108"><h3>Standard Treatment Options for NLPHL</h3><p id="CDR0000062675__1109">Standard treatment options for NLPHL include the following:</p><ol id="CDR0000062675__1110"><li class="half_rhythm"><div><a href="#CDR0000062675__1111">Radiation therapy (early stage)</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000062675__1114">Chemotherapy (advanced stage)</a>.</div></li><li class="half_rhythm"><div><a href="#CDR0000062675__1117">Rituximab</a>.</div></li></ol><div id="CDR0000062675__1111"><h4>Radiation therapy</h4><p id="CDR0000062675__1112">Based on retrospective analyses spanning several decades and because of the rarity of this histology, limited-field radiation therapy is the most-common treatment approach for patients with early-stage disease.[<a class="bk_pop" href="#CDR0000062675_rl_1104_5">5</a>-<a class="bk_pop" href="#CDR0000062675_rl_1104_8">8</a>]</p><p id="CDR0000062675__1113">Patients with nonbulky lymphocyte–predominant disease presenting in unilateral
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high neck (above the thyroid notch) or epitrochlear locations require only
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involved-field radiation therapy (IF-XRT) after clinical staging.[<a class="bk_pop" href="#CDR0000062675_rl_1104_9">9</a>] A retrospective report
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of 426 cases of lymphocyte-predominant HL (including the
|
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nodular lymphocyte–predominant and lymphocyte-rich classic
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subtypes) showed that more patients died of acute and long-term treatment-related toxicity than of recurrent HL.[<a class="bk_pop" href="#CDR0000062675_rl_1104_3">3</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335150/" class="def">Level of
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evidence: 3iiiA</a>] Limitation of radiation dose and radiation fields and avoidance of
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leukemogenic chemotherapeutic agents, along with watchful waiting policies,
|
||
should be investigated for these subgroups.[<a class="bk_pop" href="#CDR0000062675_rl_1104_10">10</a>]</p></div><div id="CDR0000062675__1114"><h4>Chemotherapy</h4><p id="CDR0000062675__1115">For patients with early-stage NLPHL, ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for two to three cycles has been combined with IF-XRT on the basis of anecdotal single-arm trials.[<a class="bk_pop" href="#CDR0000062675_rl_1104_5">5</a>,<a class="bk_pop" href="#CDR0000062675_rl_1104_11">11</a>]</p><p id="CDR0000062675__1116">For patients with advanced-stage NLPHL, chemotherapy regimens designed for patients with non-Hodgkin lymphomas may be preferred, based on two retrospective reviews and a phase II study.[<a class="bk_pop" href="#CDR0000062675_rl_1104_12">12</a>-<a class="bk_pop" href="#CDR0000062675_rl_1104_14">14</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335155/" class="def">Level of evidence: 3iiiDii</a>]</p></div><div id="CDR0000062675__1117"><h4>Rituximab</h4><p id="CDR0000062675__1118">Rituximab had a 100% response rate in a phase II trial of 39 previously untreated and relapsed NLPHL patients, most of whom had advanced-stage disease. With a median follow-up of 9.8 years, the median progression-free survival was 3.0 years for patients who received rituximab induction only and 5.6 years for patients who received rituximab induction plus rituximab maintenance.[<a class="bk_pop" href="#CDR0000062675_rl_1104_15">15</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335158/" class="def">Level of evidence: 3iiiDiii</a>] With induction only, 9 of 23 patients relapsed with an aggressive B-cell lymphoma.</p></div></div><div id="CDR0000062675__1119"><h3>Follow-Up</h3><p id="CDR0000062675__1120">Despite a usually favorable prognosis, there is a tendency for histologic transformation of NLPHL to diffuse large B-cell lymphoma or T-cell–rich large B-cell lymphoma in approximately 10% of patients by 10 years.[<a class="bk_pop" href="#CDR0000062675_rl_1104_15">15</a>,<a class="bk_pop" href="#CDR0000062675_rl_1104_16">16</a>] This propensity of NLPHL to transform to aggressive B-cell lymphoma underscores the importance of long-term follow-up and rebiopsy at relapse.[<a class="bk_pop" href="#CDR0000062675_rl_1104_15">15</a>,<a class="bk_pop" href="#CDR0000062675_rl_1104_17">17</a>]</p><p id="CDR0000062675__1121">With a median
|
||
follow-up of 7 to 8 years, more patients died of treatment-related toxic
|
||
effects (acute and long-term) than of recurrent HL. Limitation of
|
||
radiation dose and fields and avoidance of leukemogenic chemotherapeutic
|
||
agents, along with watchful waiting policies, should be investigated for these
|
||
subgroups.[<a class="bk_pop" href="#CDR0000062675_rl_1104_5">5</a>,<a class="bk_pop" href="#CDR0000062675_rl_1104_10">10</a>,<a class="bk_pop" href="#CDR0000062675_rl_1104_18">18</a>]</p><p id="CDR0000062675__1122">Relapsing disease is handled with a paradigm similar to that for a recurrent follicular lymphoma, utilizing sequential therapies and watchful waiting for some patients and considering aggressive salvage chemoimmunotherapy (like R-ICE [rituximab, ifosfamide, carboplatin, and etoposide]) followed by stem-cell transplantation for others, based on age and performance status.</p></div><div id="CDR0000062675__TrialSearch_1104_sid_9"><h3>Current Clinical Trials</h3><p id="CDR0000062675__TrialSearch_1104_22">Use our <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/advanced-search" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">advanced clinical trial search</a> to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. <a href="https://www.cancer.gov/about-cancer/treatment/clinical-trials/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">General information</a> about clinical trials is also available.</p></div><div id="CDR0000062675_rl_1104"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062675_rl_1104_1">Harris NL: Hodgkin's lymphomas: classification, diagnosis, and grading. Semin Hematol 36 (3): 220-32, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10462322" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10462322</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_2">Shimabukuro-Vornhagen A, Haverkamp H, Engert A, et al.: Lymphocyte-rich classical Hodgkin's lymphoma: clinical presentation and treatment outcome in 100 patients treated within German Hodgkin's Study Group trials. J Clin Oncol 23 (24): 5739-45, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/16009944" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16009944</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_3">Diehl V, Sextro M, Franklin J, et al.: Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease. J Clin Oncol 17 (3): 776-83, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10071266" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10071266</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_4">Nogová L, Reineke T, Brillant C, et al.: Lymphocyte-predominant and classical Hodgkin's lymphoma: a comprehensive analysis from the German Hodgkin Study Group. J Clin Oncol 26 (3): 434-9, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18086799" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18086799</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_5">Eichenauer DA, Plütschow A, Fuchs M, et al.: Long-Term Course of Patients With Stage IA Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Report From the German Hodgkin Study Group. J Clin Oncol 33 (26): 2857-62, 2015. [<a href="https://pubmed.ncbi.nlm.nih.gov/26240235" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26240235</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_6">Chen RC, Chin MS, Ng AK, et al.: Early-stage, lymphocyte-predominant Hodgkin's lymphoma: patient outcomes from a large, single-institution series with long follow-up. J Clin Oncol 28 (1): 136-41, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/19933914" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19933914</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_7">Nogová L, Reineke T, Eich HT, et al.: Extended field radiotherapy, combined modality treatment or involved field radiotherapy for patients with stage IA lymphocyte-predominant Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Study Group (GHSG). Ann Oncol 16 (10): 1683-7, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/16093276" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16093276</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_8">Wilder RB, Schlembach PJ, Jones D, et al.: European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte very favorable and favorable, lymphocyte-predominant Hodgkin disease. Cancer 94 (6): 1731-8, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11920535" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11920535</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_9">Russell KJ, Hoppe RT, Colby TV, et al.: Lymphocyte predominant Hodgkin's disease: clinical presentation and results of treatment. Radiother Oncol 1 (3): 197-205, 1984. [<a href="https://pubmed.ncbi.nlm.nih.gov/6505256" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6505256</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_10">Aster JC: Lymphocyte-predominant Hodgkin's disease: how little therapy is enough? J Clin Oncol 17 (3): 744-6, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10071261" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10071261</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_11">Savage KJ, Skinnider B, Al-Mansour M, et al.: Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome. Blood 118 (17): 4585-90, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/21873543" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21873543</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_12">Canellos GP, Mauch P: What is the appropriate systemic chemotherapy for lymphocyte-predominant Hodgkin's lymphoma? J Clin Oncol 28 (1): e8, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/19933898" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19933898</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_13">Xing KH, Connors JM, Lai A, et al.: Advanced-stage nodular lymphocyte predominant Hodgkin lymphoma compared with classical Hodgkin lymphoma: a matched pair outcome analysis. Blood 123 (23): 3567-73, 2014. [<a href="https://pubmed.ncbi.nlm.nih.gov/24713929" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24713929</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_14">Fanale MA, Cheah CY, Rich A, et al.: Encouraging activity for R-CHOP in advanced stage nodular lymphocyte-predominant Hodgkin lymphoma. Blood 130 (4): 472-477, 2017. [<a href="/pmc/articles/PMC5578726/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5578726</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28522441" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28522441</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_15">Advani RH, Horning SJ, Hoppe RT, et al.: Mature results of a phase II study of rituximab therapy for nodular lymphocyte-predominant Hodgkin lymphoma. J Clin Oncol 32 (9): 912-8, 2014. [<a href="https://pubmed.ncbi.nlm.nih.gov/24516013" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24516013</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_16">Al-Mansour M, Connors JM, Gascoyne RD, et al.: Transformation to aggressive lymphoma in nodular lymphocyte-predominant Hodgkin's lymphoma. J Clin Oncol 28 (5): 793-9, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20048177" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20048177</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_17">Kenderian SS, Habermann TM, Macon WR, et al.: Large B-cell transformation in nodular lymphocyte-predominant Hodgkin lymphoma: 40-year experience from a single institution. Blood 127 (16): 1960-6, 2016. [<a href="/pmc/articles/PMC4841039/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4841039</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26837698" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26837698</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_1104_18">Pellegrino B, Terrier-Lacombe MJ, Oberlin O, et al.: Lymphocyte-predominant Hodgkin's lymphoma in children: therapeutic abstention after initial lymph node resection--a Study of the French Society of Pediatric Oncology. J Clin Oncol 21 (15): 2948-52, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12885814" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12885814</span></a>]</div></li></ol></div></div><div id="CDR0000062675__448"><h2 id="_CDR0000062675__448_">HL During Pregnancy</h2><div id="CDR0000062675__449"><h3>Introduction</h3><p id="CDR0000062675__450">Hodgkin lymphoma (HL) affects primarily young women, some of whom may be pregnant. When treating a pregnant woman, an oncologist will provide therapy that minimizes risk to the fetus. Treatment choice must be individualized,
|
||
taking into consideration the following:</p><ul id="CDR0000062675__957"><li class="half_rhythm"><div>The mother’s wishes.</div></li><li class="half_rhythm"><div>The severity and aggressiveness of the
|
||
HL.</div></li><li class="half_rhythm"><div>The trimester of the pregnancy.</div></li></ul></div><div id="CDR0000062675__451"><h3>Stage Information for HL During Pregnancy</h3><p id="CDR0000062675__452">To avoid exposing a pregnant woman to ionizing
|
||
radiation, magnetic resonance imaging
|
||
is the preferred method for staging evaluation.[<a class="bk_pop" href="#CDR0000062675_rl_448_1">1</a>] The presenting stage, clinical behavior, prognosis, and histologic subtypes of HL in pregnant women do not differ from those in nonpregnant women during their childbearing years.[<a class="bk_pop" href="#CDR0000062675_rl_448_2">2</a>] Refer to the <a href="#CDR0000062675__12">Stage Information for Adult HL</a> section of this summary for more information about staging HL.</p></div><div id="CDR0000062675__453"><h3>Treatment Options for HL During Pregnancy</h3><p id="CDR0000062675__851">Treatment options for HL during pregnancy include the following:</p><ol id="CDR0000062675__938"><li class="half_rhythm"><div>Watchful waiting.</div></li><li class="half_rhythm"><div>Radiation therapy.</div></li><li class="half_rhythm"><div>Chemotherapy.</div></li></ol><p id="CDR0000062675__916">In one study, the 20-year survival rate of pregnant women with HL did not differ from the 20-year survival rate of nonpregnant women who were matched for similar stage of disease, age at diagnosis, and calendar year of treatment.[<a class="bk_pop" href="#CDR0000062675_rl_448_3">3</a>] </p><p id="CDR0000062675__981">The long-term effects on progeny after chemotherapy in utero are unknown, although evidence tends to be promising.[<a class="bk_pop" href="#CDR0000062675_rl_448_3">3</a>-<a class="bk_pop" href="#CDR0000062675_rl_448_7">7</a>]</p><p id="CDR0000062675__982"> There is no evidence that a pregnancy after completion of therapy increases the relapse rate for patients in remission.[<a class="bk_pop" href="#CDR0000062675_rl_448_8">8</a>]</p><div id="CDR0000062675__853"><h4>Therapy during the first trimester</h4><p id="CDR0000062675__454">HL that is diagnosed in the first trimester of pregnancy does not constitute an absolute indication for therapeutic abortion. Treatment options for each patient must take into account disease stage, rapidity of growth of the lymphoma, and the patient's wishes.[<a class="bk_pop" href="#CDR0000062675_rl_448_9">9</a>] </p><div id="CDR0000062675__983"><h5>Watchful waiting</h5><p id="CDR0000062675__984">If the HL presents in
|
||
early stage above the diaphragm and appears to be growing slowly, patients can
|
||
be observed carefully, with plans to induce delivery early and proceed with
|
||
definitive therapy.[<a class="bk_pop" href="#CDR0000062675_rl_448_10">10</a>]</p></div><div id="CDR0000062675__985"><h5>Radiation therapy</h5><p id="CDR0000062675__854">Alternatively, these patients can receive radiation
|
||
therapy with proper shielding.[<a class="bk_pop" href="#CDR0000062675_rl_448_11">11</a>-<a class="bk_pop" href="#CDR0000062675_rl_448_14">14</a>] Investigators at the MD Anderson Cancer Center reported no
|
||
congenital abnormalities in 16 babies delivered after the mothers had received
|
||
supradiaphragmatic radiation while the uterus was shielded with five half-value
|
||
layers of lead.[<a class="bk_pop" href="#CDR0000062675_rl_448_15">15</a>] Because of theoretical risks of the fetus developing future malignancies from even minimal scattered radiation doses outside the radiation field, postponing radiation therapy—if possible, until after delivery—should be considered.[<a class="bk_pop" href="#CDR0000062675_rl_448_16">16</a>]</p></div><div id="CDR0000062675__986"><h5>Chemotherapy</h5><p id="CDR0000062675__987">Evidence (chemotherapy during the first trimester):</p><ol id="CDR0000062675__988"><li class="half_rhythm"><div>Chemotherapy that is administered in the first trimester has been
|
||
associated with congenital abnormalities in as many as 33% of infants.[<a class="bk_pop" href="#CDR0000062675_rl_448_4">4</a>,<a class="bk_pop" href="#CDR0000062675_rl_448_17">17</a>]
|
||
Consequently, some
|
||
women may opt to continue the pregnancy and agree to radiation therapy or
|
||
chemotherapy if immediate treatment is required after the first trimester.</div></li><li class="half_rhythm"><div>A multicenter retrospective analysis of 40 patients described pregnancy termination in 3 patients, deferral of therapy to postpartum in 13 patients (median 30-week gestation), and antenatal therapy applied to the remaining 24 patients (median 21-week gestation, all done after the first trimester).[<a class="bk_pop" href="#CDR0000062675_rl_448_18">18</a>]<ul id="CDR0000062675__989"><li class="half_rhythm"><div>With a median follow-up of 41 months, the 3-year progression-free survival (PFS) rate was 85%, and the overall survival (OS) rate was 97%, often with the use of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine).[<a class="bk_pop" href="#CDR0000062675_rl_448_18">18</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>]</div></li></ul></div></li><li class="half_rhythm"><div>A retrospective analysis of 39 patients from the MD Anderson Cancer Center described pregnancy termination in 3 patients, deferral of therapy to the postpartum period in 12 patients, and antenatal therapy applied to 24 patients.[<a class="bk_pop" href="#CDR0000062675_rl_448_19">19</a>]<ul id="CDR0000062675__990"><li class="half_rhythm"><div>Two women miscarried after receiving doxorubicin-based chemotherapy in the first trimester.</div></li><li class="half_rhythm"><div>With a median follow-up of 68 months from diagnosis, the 5-year PFS rate was 75%, and the OS rate was 82%. These rates did not differ between the antenatal and postpartum timing of therapy.[<a class="bk_pop" href="#CDR0000062675_rl_448_19">19</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>] </div></li></ul></div></li></ol></div></div><div id="CDR0000062675__855"><h4>Therapy later in pregnancy</h4><div id="CDR0000062675__991"><h5>Watchful waiting</h5><p id="CDR0000062675__992">In the second half of pregnancy, patients can be observed carefully,
|
||
and therapy can be postponed until induction of delivery at 32 to 36 weeks.[<a class="bk_pop" href="#CDR0000062675_rl_448_6">6</a>,<a class="bk_pop" href="#CDR0000062675_rl_448_7">7</a>,<a class="bk_pop" href="#CDR0000062675_rl_448_17">17</a>]</p></div><div id="CDR0000062675__994"><h5>Radiation therapy</h5><p id="CDR0000062675__856">As an
|
||
alternative, a short course of radiation therapy can be used before delivery in
|
||
cases of respiratory compromise caused by a rapidly enlarging mediastinal mass.</p></div><div id="CDR0000062675__993"><h5>Chemotherapy</h5><p id="CDR0000062675__456"> If
|
||
chemotherapy is mandatory before delivery—such as for patients with
|
||
symptomatic advanced-stage disease—vinblastine alone, given intravenously at 6 mg/m² every 2 weeks until induction of delivery, may
|
||
be considered because it has not been associated with fetal abnormalities in the
|
||
second half of pregnancy.[<a class="bk_pop" href="#CDR0000062675_rl_448_6">6</a>,<a class="bk_pop" href="#CDR0000062675_rl_448_7">7</a>] Combination chemotherapy with ABVD appears to be safe in the second half of pregnancy.[<a class="bk_pop" href="#CDR0000062675_rl_448_5">5</a>] If chemotherapy is required after the first trimester, many clinicians prefer the combination of drugs over single-agent drugs or radiation therapy. Steroids are employed both for their
|
||
antitumor effect and for hastening fetal pulmonary maturity.</p></div></div></div><div id="CDR0000062675_rl_448"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062675_rl_448_1">Nicklas AH, Baker ME: Imaging strategies in the pregnant cancer patient. Semin Oncol 27 (6): 623-32, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/11130469" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11130469</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_2">Gelb AB, van de Rijn M, Warnke RA, et al.: Pregnancy-associated lymphomas. A clinicopathologic study. Cancer 78 (2): 304-10, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8674008" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8674008</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_3">Lishner M, Zemlickis D, Degendorfer P, et al.: Maternal and foetal outcome following Hodgkin's disease in pregnancy. Br J Cancer 65 (1): 114-7, 1992. [<a href="/pmc/articles/PMC1977347/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1977347</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/1733434" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1733434</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_4">Thomas PR, Biochem D, Peckham MJ: The investigation and management of Hodgkin's disease in the pregnant patient. Cancer 38 (3): 1443-51, 1976. [<a href="https://pubmed.ncbi.nlm.nih.gov/953978" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 953978</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_5">Avilés A, Díaz-Maqueo JC, Talavera A, et al.: Growth and development of children of mothers treated with chemotherapy during pregnancy: current status of 43 children. Am J Hematol 36 (4): 243-8, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1707227" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1707227</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_6">Jacobs C, Donaldson SS, Rosenberg SA, et al.: Management of the pregnant patient with Hodgkin's disease. Ann Intern Med 95 (6): 669-75, 1981. [<a href="https://pubmed.ncbi.nlm.nih.gov/7305142" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7305142</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_7">Nisce LZ, Tome MA, He S, et al.: Management of coexisting Hodgkin's disease and pregnancy. Am J Clin Oncol 9 (2): 146-51, 1986. [<a href="https://pubmed.ncbi.nlm.nih.gov/3717081" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3717081</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_8">Weibull CE, Eloranta S, Smedby KE, et al.: Pregnancy and the Risk of Relapse in Patients Diagnosed With Hodgkin Lymphoma. J Clin Oncol 34 (4): 337-44, 2016. [<a href="https://pubmed.ncbi.nlm.nih.gov/26668344" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26668344</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_9">Koren G, Weiner L, Lishner M, et al.: Cancer in pregnancy: identification of unanswered questions on maternal and fetal risks. Obstet Gynecol Surv 45 (8): 509-14, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2198503" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2198503</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_10">Anselmo AP, Cavalieri E, Enrici RM, et al.: Hodgkin's disease during pregnancy: diagnostic and therapeutic management. Fetal Diagn Ther 14 (2): 102-5, 1999 Mar-Apr. [<a href="https://pubmed.ncbi.nlm.nih.gov/10085508" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10085508</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_11">Mazonakis M, Varveris H, Fasoulaki M, et al.: Radiotherapy of Hodgkin's disease in early pregnancy: embryo dose measurements. Radiother Oncol 66 (3): 333-9, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12742274" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12742274</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_12">Greskovich JF Jr, Macklis RM: Radiation therapy in pregnancy: risk calculation and risk minimization. Semin Oncol 27 (6): 633-45, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/11130470" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11130470</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_13">Fisher PM, Hancock BW: Hodgkin's disease in the pregnant patient. Br J Hosp Med 56 (10): 529-32, 1996 Nov 20-Dec 10. [<a href="https://pubmed.ncbi.nlm.nih.gov/8958407" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8958407</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_14">Friedman E, Jones GW: Fetal outcome after maternal radiation treatment of supradiaphragmatic Hodgkin's disease. CMAJ 149 (9): 1281-3, 1993. [<a href="/pmc/articles/PMC1485698/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1485698</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/8221483" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8221483</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_15">Woo SY, Fuller LM, Cundiff JH, et al.: Radiotherapy during pregnancy for clinical stages IA-IIA Hodgkin's disease. Int J Radiat Oncol Biol Phys 23 (2): 407-12, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1587764" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1587764</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_16">Lishner M: Cancer in pregnancy. Ann Oncol 14 (Suppl 3): iii31-6, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12821536" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12821536</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_17">Cardonick E, Iacobucci A: Use of chemotherapy during human pregnancy. Lancet Oncol 5 (5): 283-91, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15120665" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15120665</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_18">Evens AM, Advani R, Press OW, et al.: Lymphoma occurring during pregnancy: antenatal therapy, complications, and maternal survival in a multicenter analysis. J Clin Oncol 31 (32): 4132-9, 2013. [<a href="https://pubmed.ncbi.nlm.nih.gov/24043736" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24043736</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062675_rl_448_19">Pinnix CC, Osborne EM, Chihara D, et al.: Maternal and Fetal Outcomes After Therapy for Hodgkin or Non-Hodgkin Lymphoma Diagnosed During Pregnancy. JAMA Oncol 2 (8): 1065-9, 2016. [<a href="/pmc/articles/PMC7457973/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7457973</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27227654" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27227654</span></a>]</div></li></ol></div></div><div id="CDR0000062675__207"><h2 id="_CDR0000062675__207_">Changes to This Summary (08/15/2018)</h2><p id="CDR0000062675__208">The PDQ cancer information summaries are reviewed regularly and updated as
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new information becomes available. This section describes the latest
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changes made to this summary as of the date above.</p><p id="CDR0000062675__858">This summary was comprehensively reviewed, extensively revised, and reformatted.</p><p id="CDR0000062675__disclaimerHP_3">This summary is written and maintained by the <a href="https://www.cancer.gov/publications/pdq/editorial-boards/adult-treatment" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Adult Treatment Editorial Board</a>, which is
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editorially independent of NCI. The summary reflects an independent review of
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the literature and does not represent a policy statement of NCI or NIH. More
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information about summary policies and the role of the PDQ Editorial Boards in
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maintaining the PDQ summaries can be found on the <a href="#CDR0000062675__AboutThis_1">About This PDQ Summary</a> and <a href="https://www.cancer.gov/publications/pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ® - NCI's Comprehensive Cancer Database</a> pages.
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</p></div><div id="CDR0000062675__AboutThis_1"><h2 id="_CDR0000062675__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000062675__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000062675__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult Hodgkin lymphoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.</p></div><div id="CDR0000062675__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000062675__AboutThis_5">This summary is reviewed regularly and updated as necessary by the <a href="https://www.cancer.gov/publications/pdq/editorial-boards/adult-treatment" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">PDQ Adult Treatment Editorial Board</a>, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).</p><p id="CDR0000062675__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000062675__AboutThis_6"><li class="half_rhythm"><div>be discussed at a meeting,</div></li><li class="half_rhythm"><div>be cited with text, or</div></li><li class="half_rhythm"><div>replace or update an existing article that is already cited.</div></li></ul><p id="CDR0000062675__AboutThis_7">Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.</p><p>The lead reviewer for Adult Hodgkin Lymphoma Treatment is:</p><ul><li class="half_rhythm"><div>Eric J. Seifter, MD (Johns Hopkins University)</div></li></ul><p id="CDR0000062675__AboutThis_9">Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.</p></div><div id="CDR0000062675__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000062675__AboutThis_11">Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a <a href="/books/n/pdqcis/CDR0000062796/">formal evidence ranking system</a> in developing its level-of-evidence designations.</p></div><div id="CDR0000062675__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000062675__AboutThis_13">PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”</p><p id="CDR0000062675__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000062675__AboutThis_15">PDQ® Adult Treatment Editorial Board. PDQ Adult Hodgkin Lymphoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: <a href="https://www.cancer.gov/types/lymphoma/hp/adult-hodgkin-treatment-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www.cancer.gov/types/lymphoma/hp/adult-hodgkin-treatment-pdq</a>. Accessed <MM/DD/YYYY>. [PMID: 26389473]</p><p id="CDR0000062675__AboutThis_16">Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in <a href="https://visualsonline.cancer.gov/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Visuals Online</a>, a collection of over 2,000 scientific images.
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</p></div><div id="CDR0000062675__AboutThis_17"><h3>Disclaimer</h3><p id="CDR0000062675__AboutThis_18">Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the <a href="https://www.cancer.gov/about-cancer/managing-care" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Managing Cancer Care</a> page.</p></div><div id="CDR0000062675__AboutThis_20"><h3>Contact Us</h3><p id="CDR0000062675__AboutThis_21">More information about contacting us or receiving help with the Cancer.gov website can be found on our <a href="https://www.cancer.gov/contact" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Contact Us for Help</a> page. Questions can also be submitted to Cancer.gov through the website’s <a href="https://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>.</p></div></div></div></div>
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<div xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Views</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="PDF_download" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK66038.13/?report=reader">PubReader</a></li><li><a href="/books/NBK66038.13/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK66038" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK66038" style="display:none" title="Cite this Page"><div class="bk_tt">PDQ Adult Treatment Editorial Board. 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2016</li><li><span class="bk_col_itm"><a href="/books/NBK66038.4/">NBK66038.4</a></span> January 15, 2016</li><li><span class="bk_col_itm"><a href="/books/NBK66038.3/">NBK66038.3</a></span> November 5, 2015</li><li><span class="bk_col_itm"><a href="/books/NBK66038.2/">NBK66038.2</a></span> September 25, 2015</li><li><span class="bk_col_itm"><a href="/books/NBK66038.1/">NBK66038.1</a></span> August 12, 2015</li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>In this Page</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="page-toc" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="#CDR0000062675__1" ref="log$=inpage&link_id=inpage">General Information About Adult Hodgkin Lymphoma (HL)</a></li><li><a href="#CDR0000062675__295" ref="log$=inpage&link_id=inpage">Cellular Classification of Adult HL</a></li><li><a href="#CDR0000062675__12" ref="log$=inpage&link_id=inpage">Stage Information for Adult HL</a></li><li><a href="#CDR0000062675__36" ref="log$=inpage&link_id=inpage">Treatment Option Overview for Adult HL</a></li><li><a href="#CDR0000062675__362" ref="log$=inpage&link_id=inpage">Early Favorable Classic HL Treatment</a></li><li><a href="#CDR0000062675__373" ref="log$=inpage&link_id=inpage">Early Unfavorable Classic HL Treatment</a></li><li><a href="#CDR0000062675__402" ref="log$=inpage&link_id=inpage">Advanced Classic HL Treatment</a></li><li><a href="#CDR0000062675__174" ref="log$=inpage&link_id=inpage">Recurrent Adult Classic HL Treatment</a></li><li><a href="#CDR0000062675__1104" ref="log$=inpage&link_id=inpage">Nodular Lymphocyte–Predominant HL (NLPHL) Treatment</a></li><li><a href="#CDR0000062675__448" ref="log$=inpage&link_id=inpage">HL During Pregnancy</a></li><li><a href="#CDR0000062675__207" ref="log$=inpage&link_id=inpage">Changes to This Summary (08/15/2018)</a></li><li><a href="#CDR0000062675__AboutThis_1" ref="log$=inpage&link_id=inpage">About This PDQ Summary</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related publications</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK65804/">Patient Version</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" 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Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389170" ref="ordinalpos=1&linkpos=2&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Childhood Hodgkin Lymphoma Treatment (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Childhood Hodgkin Lymphoma Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Pediatric Treatment Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/37437081" ref="ordinalpos=1&linkpos=3&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Non-Hodgkin Lymphoma Treatment During Pregnancy (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Non-Hodgkin Lymphoma Treatment During Pregnancy (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Adult Treatment Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/37437080" ref="ordinalpos=1&linkpos=4&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> B-Cell Non-Hodgkin Lymphoma Treatment (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> B-Cell Non-Hodgkin Lymphoma Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Adult Treatment Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/37437079" ref="ordinalpos=1&linkpos=5&log$=relatedreviews&logdbfrom=pubmed"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Peripheral T-Cell Non-Hodgkin Lymphoma Treatment (PDQ®): Health Professional Version.</a><span class="source">[PDQ Cancer Information Summari...]</span><div class="brieflinkpop offscreen_noflow"><span xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="invert">Review</span> Peripheral T-Cell Non-Hodgkin Lymphoma Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="author">PDQ Adult Treatment Editorial Board. </em><em xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li></ul><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed_reviews&uid=26389473" ref="ordinalpos=1&log$=relatedreviews_seeall&logdbfrom=pubmed">See reviews...</a><a class="seemore" href="/sites/entrez?db=pubmed&cmd=link&linkname=pubmed_pubmed&uid=26389473" ref="ordinalpos=1&log$=relatedarticles_seeall&logdbfrom=pubmed">See all...</a></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Recent Activity</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" 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