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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="#__NBK65743_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK65743_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="_NBK65743_"><span class="title" itemprop="name">AIDS-Related 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: April 2, 2015.</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="CDR0000062940__162">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of AIDS-related 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="CDR0000062940__163">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="CDR0000062940__1"><h2 id="_CDR0000062940__1_">General Information About AIDS-Related Lymphoma</h2><div id="CDR0000062940__151"><h3>Background and Definitions</h3><p id="CDR0000062940__2">The AIDS was first described in 1981, and
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the first definitions included certain opportunistic infections, Kaposi
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sarcoma, and central nervous system (CNS) lymphomas.
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In 1984, a multicenter
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study described the clinical spectrum of non-Hodgkin lymphomas (NHLs) in the
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populations at risk for AIDS.[<a class="bk_pop" href="#CDR0000062940_rl_1_1">1</a>] In 1985 and 1987, the Centers for Disease
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|
Control and Prevention (CDC) revised the definition of AIDS to include human immunodeficiency
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virus (HIV)-infected patients who had aggressive B-cell NHL.
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The incidence of NHL has increased in an almost parallel
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course with the AIDS epidemic and accounts for 2% to 3% of newly diagnosed AIDS
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cases.[<a class="bk_pop" href="#CDR0000062940_rl_1_2">2</a>]
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</p></div><div id="CDR0000062940__152"><h3>Histology</h3><p id="CDR0000062940__3">Pathologically, AIDS-related lymphomas are comprised of a narrow spectrum of
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histologic types consisting almost exclusively of B-cell tumors of aggressive
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type. These include the following:
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</p><ul id="CDR0000062940__46"><li class="half_rhythm"><div>Diffuse large B-cell lymphoma.</div></li><li class="half_rhythm"><div>B-cell immunoblastic lymphoma.</div></li><li class="half_rhythm"><div>Small
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noncleaved lymphoma, either Burkitt or Burkitt-like.</div></li></ul><p id="CDR0000062940__61">The HIV-associated lymphomas
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can be categorized into the following:</p><ul id="CDR0000062940__48"><li class="half_rhythm"><div>Aggressive B-cell lymphoma.</div></li><li class="half_rhythm"><div>Primary central nervous system lymphoma (PCNSL),
|
|
which represents 20% of all NHL cases in AIDS patients. </div></li><li class="half_rhythm"><div>Primary effusion lymphoma.</div></li><li class="half_rhythm"><div>Plasmablastic multicentric Castleman disease.</div></li><li class="half_rhythm"><div>Hodgkin lymphoma.</div></li></ul><div id="CDR0000062940__153"><h4>Primary effusion lymphoma</h4><p id="CDR0000062940__49">Primary effusion lymphoma has been associated with Kaposi
|
|
sarcoma-associated herpes-virus/human herpes virus type-8 (KSHV/HHV-8).[<a class="bk_pop" href="#CDR0000062940_rl_1_3">3</a>,<a class="bk_pop" href="#CDR0000062940_rl_1_4">4</a>]
|
|
Primary effusion lymphoma presents as a liquid phase spreading along serous membranes in the absence of masses or adenopathy.[<a class="bk_pop" href="#CDR0000062940_rl_1_3">3</a>] In addition to HHV-8, many cases are also associated with Epstein-Barr virus. Extension of lymphoma from the effusion to underlying tissue may occur. Plasmablastic multicentric Castleman disease is also associated with a coinfection of KSHV/HHV-8 and HIV.[<a class="bk_pop" href="#CDR0000062940_rl_1_5">5</a>,<a class="bk_pop" href="#CDR0000062940_rl_1_6">6</a>] Patients typically present with fever, night sweats, weight loss, lymphadenopathy, and hepatosplenomegaly. Patients may progress to primary effusion lymphoma or to plasmablastic or anaplastic large cell lymphoma. Anecdotal responses to rituximab, an anti-CD20 monoclonal antibody, have been reported.[<a class="bk_pop" href="#CDR0000062940_rl_1_5">5</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>]</p></div></div><div id="CDR0000062940__154"><h3>Incidence and Prevention</h3><p id="CDR0000062940__4">An international database of 48,000 HIV-seropositive individuals from the
|
|
United States, Europe, and Australia found a 42% decline in the incidence of
|
|
NHLs from 1997 to 1999 compared with 1992 to 1996, both for
|
|
PCNSL and for systemic lymphoma.[<a class="bk_pop" href="#CDR0000062940_rl_1_7">7</a>] The introduction of highly active
|
|
antiretroviral therapy (HAART) is the proposed explanation for this decline.[<a class="bk_pop" href="#CDR0000062940_rl_1_8">8</a>] The diagnosis of AIDS precedes the onset of
|
|
NHL in approximately 57% of the patients, but in 30% of the patients the
|
|
diagnosis of AIDS is made at the time of the diagnosis of NHL and HIV positivity.[<a class="bk_pop" href="#CDR0000062940_rl_1_9">9</a>] The geographic distribution of these lymphomas
|
|
is also similar to the geographic spread of AIDS. Unlike Kaposi sarcoma,
|
|
which has a predilection for homosexual men and appears to be on the decline in
|
|
incidence, all risk groups appear to have an excess number of NHLs; these risk groups include intravenous drug users and children of
|
|
HIV-positive individuals.
|
|
</p></div><div id="CDR0000062940__155"><h3>Clinical Presentation</h3><p id="CDR0000062940__116">In general, the clinical setting and response to treatment of patients with
|
|
AIDS-related lymphoma is very different from that of the non-HIV patients with
|
|
lymphoma. The HIV-infected individual with aggressive lymphoma usually
|
|
presents with advanced-stage disease that is frequently extranodal.[<a class="bk_pop" href="#CDR0000062940_rl_1_10">10</a>]</p><p id="CDR0000062940__117">Common extranodal sites include the following:</p><ul id="CDR0000062940__118"><li class="half_rhythm"><div>Bone marrow.</div></li><li class="half_rhythm"><div>Liver.</div></li><li class="half_rhythm"><div>Meninges.</div></li><li class="half_rhythm"><div>Gastrointestinal tract.</div></li></ul><p id="CDR0000062940__119">Very unusual sites are also characteristic and include the following:</p><ul id="CDR0000062940__120"><li class="half_rhythm"><div>Anus.</div></li><li class="half_rhythm"><div>Heart.</div></li><li class="half_rhythm"><div>Bile duct.</div></li><li class="half_rhythm"><div>Gingiva.</div></li><li class="half_rhythm"><div>Muscles.</div></li></ul><p id="CDR0000062940__5">
|
|
The clinical course is
|
|
more aggressive, and the disease is both more extensive and less responsive to
|
|
chemotherapy. Immunodeficiency and cytopenias, common in these patients at the
|
|
time of initial presentation, are exacerbated by the administration of
|
|
chemotherapy. Treatment of the malignancy increases the risk of
|
|
opportunistic infections that, in turn, further compromise the delivery of
|
|
adequate treatment.
|
|
</p></div><div id="CDR0000062940__156"><h3>Prognosis and Survival</h3><p id="CDR0000062940__121">Prognoses of patients with AIDS-related lymphoma have been associated with the following:[<a class="bk_pop" href="#CDR0000062940_rl_1_11">11</a>]</p><ul id="CDR0000062940__122"><li class="half_rhythm"><div>Stage (i.e., extent of disease, extranodal involvement, lactate dehydrogenase level, and bone marrow involvement).</div></li><li class="half_rhythm"><div>Age.</div></li><li class="half_rhythm"><div>Severity of the underlying immunodeficiency (measured by CD4 lymphocyte count
|
|
in peripheral blood).</div></li><li class="half_rhythm"><div>Performance status.</div></li><li class="half_rhythm"><div>Prior AIDS diagnosis (i.e., history of opportunistic infection or Kaposi sarcoma).</div></li></ul><p id="CDR0000062940__6"> Patients with AIDS-related
|
|
PCNSL appear to have more severe underlying HIV-related disease
|
|
than do patients with systemic lymphoma. In one report, this severity was
|
|
evidenced by patients with PCNSL having a higher incidence of
|
|
prior AIDS diagnoses (73% vs. 37%), lower median number of CD4 lymphocytes
|
|
(30/dL vs. 189/dL), and a worse median survival time (2.5 months vs. 6.0
|
|
months).[<a class="bk_pop" href="#CDR0000062940_rl_1_12">12</a>] This report also showed that patients with poor risk factors—defined as Karnofsky performance status less than 70%, history of prior AIDS
|
|
diagnosis, and bone marrow involvement—had a median survival time of 4.0
|
|
months compared with a good prognosis group without any of these risk factors,
|
|
who had a median survival time of 11.3 months. </p><p id="CDR0000062940__67">In another report (NIAID-ACTG-142), prognostic
|
|
factors were evaluated in a group of 192 patients with newly diagnosed
|
|
AIDS-related lymphoma who were randomly assigned to receive either low-dose
|
|
methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and
|
|
dexamethasone (m-BACOD) or standard dose m-BACOD with granulocyte-macrophage
|
|
colony-stimulating factor.[<a class="bk_pop" href="#CDR0000062940_rl_1_13">13</a>] No differences existed between these two
|
|
treatments in terms of efficacy for disease-free survival, median survival, or
|
|
risk ratio for death.[<a class="bk_pop" href="#CDR0000062940_rl_1_13">13</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] On multivariate analysis,
|
|
factors associated with decreased survival included age older than 35 years,
|
|
history of intravenous drug use, stage III or stage IV disease, and CD4 counts of
|
|
less than 100 cells/mm<sup>3</sup>. The median survival rates were 46
|
|
weeks for patients with one or no risk factors, 44 weeks for patients with two risk
|
|
factors, and 18 weeks for patients with three or more risk factors. The
|
|
International Prognostic Index may also be predictive for survival.[<a class="bk_pop" href="#CDR0000062940_rl_1_14">14</a>-<a class="bk_pop" href="#CDR0000062940_rl_1_16">16</a>]
|
|
In a multicenter cohort study of 203 patients, in a multivariable Cox model, response to HAART was independently associated with prolonged survival (relative hazard = 0.32; 95% confidence interval, 0.16–0.62).[<a class="bk_pop" href="#CDR0000062940_rl_1_17">17</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335155/" class="def">Level of evidence: 3iiiDii</a>]</p><p id="CDR0000062940__86"><b><div class="milestone-start" id="CDR0000062940__7"></div>HIV-associated Hodgkin lymphoma</b></p><p id="CDR0000062940__8">Multiple reviews of Hodgkin lymphoma occurring in patients
|
|
at risk for AIDS have been done;[<a class="bk_pop" href="#CDR0000062940_rl_1_18">18</a>,<a class="bk_pop" href="#CDR0000062940_rl_1_19">19</a>] however, Hodgkin lymphoma is still
|
|
not part of the CDC definition of AIDS because of no clear
|
|
demonstration of its increased incidence in conjunction with HIV, as is the
|
|
case for aggressive NHL. The CDC, in conjunction with the
|
|
San Francisco Department of Public Health, has reported a cohort study in which
|
|
HIV-infected men had an excess risk that was attributable to the HIV infection
|
|
of 19.3 cases of Hodgkin lymphoma per 100,000 person-years and 224.9 cases of
|
|
NHL per 100,000 person-years. Although an excess incidence
|
|
of Hodgkin lymphoma was found in HIV-infected homosexual men in this report,
|
|
additional epidemiologic studies will be needed before the CDC will reconsider
|
|
Hodgkin lymphoma as an HIV-associated malignancy.[<a class="bk_pop" href="#CDR0000062940_rl_1_20">20</a>]
|
|
</p><p id="CDR0000062940__9">HIV-associated Hodgkin lymphoma presents in an aggressive fashion, often with
|
|
extranodal or bone marrow involvement.[<a class="bk_pop" href="#CDR0000062940_rl_1_18">18</a>,<a class="bk_pop" href="#CDR0000062940_rl_1_19">19</a>,<a class="bk_pop" href="#CDR0000062940_rl_1_21">21</a>] A distinctive feature of
|
|
HIV-associated Hodgkin lymphoma is the lower frequency of mediastinal
|
|
adenopathy compared with non-HIV-associated Hodgkin lymphoma. Most patients in
|
|
these series had either mixed cellularity or lymphocyte-depleted Hodgkin
|
|
lymphoma, expression of Epstein-Barr virus-associated proteins in Reed-Sternberg cells, B symptoms, and a median CD4 lymphocyte count of 300/dL or
|
|
less.[<a class="bk_pop" href="#CDR0000062940_rl_1_22">22</a>]
|
|
In a retrospective multicenter review of 62 patients, those receiving HAART with chemotherapy had a 74% 2-year overall survival (OS) versus a 30% OS for those not receiving HAART (<i>P</i> < .001).[<a class="bk_pop" href="#CDR0000062940_rl_1_23">23</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335150/" class="def">Level of evidence: 3iiiA</a>]<div class="milestone-end"></div></p></div><div id="CDR0000062940__133"><h3>Related Summaries</h3><p id="CDR0000062940__134">Note: Other PDQ summaries containing information about AIDS-related lymphoma include the following: </p><ul id="CDR0000062940__135"><li class="half_rhythm"><div><a href="/books/n/pdqcis/CDR0000062914/">Kaposi Sarcoma</a></div></li><li class="half_rhythm"><div><a href="/books/n/pdqcis/CDR0000062768/">Primary CNS Lymphoma</a></div></li></ul></div><div id="CDR0000062940_rl_1"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062940_rl_1_1">Ziegler JL, Beckstead JA, Volberding PA, et al.: Non-Hodgkin's lymphoma in 90 homosexual men. Relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome. N Engl J Med 311 (9): 565-70, 1984. [<a href="https://pubmed.ncbi.nlm.nih.gov/6611504" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6611504</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_2">Rabkin CS, Yellin F: Cancer incidence in a population with a high prevalence of infection with human immunodeficiency virus type 1. J Natl Cancer Inst 86 (22): 1711-6, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7966400" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7966400</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_3">Simonelli C, Spina M, Cinelli R, et al.: Clinical features and outcome of primary effusion lymphoma in HIV-infected patients: a single-institution study. J Clin Oncol 21 (21): 3948-54, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/14581418" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14581418</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_4">Nador RG, Cesarman E, Chadburn A, et al.: Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus. Blood 88 (2): 645-56, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8695812" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8695812</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_5">Goedert JJ: Multicentric Castleman disease: viral and cellular targets for intervention. Blood 102 (8): 2710-11, 2003.</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_6">Marcelin AG, Aaron L, Mateus C, et al.: Rituximab therapy for HIV-associated Castleman disease. Blood 102 (8): 2786-8, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12842986" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12842986</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_7">International Collaboration on HIV and Cancer: Highly active antiretroviral therapy and incidence of cancer in human immunodeficiency virus-infected adults. J Natl Cancer Inst 92 (22): 1823-30, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/11078759" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11078759</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_8">Stebbing J, Gazzard B, Mandalia S, et al.: Antiretroviral treatment regimens and immune parameters in the prevention of systemic AIDS-related non-Hodgkin's lymphoma. J Clin Oncol 22 (11): 2177-83, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15169806" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15169806</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_9">Knowles DM, Chamulak GA, Subar M, et al.: Lymphoid neoplasia associated with the acquired immunodeficiency syndrome (AIDS). The New York University Medical Center experience with 105 patients (1981-1986). Ann Intern Med 108 (5): 744-53, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3358573" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3358573</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_10">Sparano JA: Clinical aspects and management of AIDS-related lymphoma. Eur J Cancer 37 (10): 1296-305, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11423261" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11423261</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_11">Bower M, Gazzard B, Mandalia S, et al.: A prognostic index for systemic AIDS-related non-Hodgkin lymphoma treated in the era of highly active antiretroviral therapy. Ann Intern Med 143 (4): 265-73, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/16103470" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16103470</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_12">Levine AM, Sullivan-Halley J, Pike MC, et al.: Human immunodeficiency virus-related lymphoma. Prognostic factors predictive of survival. Cancer 68 (11): 2466-72, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1933784" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1933784</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_13">Kaplan LD, Straus DJ, Testa MA, et al.: Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med 336 (23): 1641-8, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9171066" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9171066</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_14">Navarro JT, Ribera JM, Oriol A, et al.: International prognostic index is the best prognostic factor for survival in patients with AIDS-related non-Hodgkin's lymphoma treated with CHOP. A multivariate study of 46 patients. Haematologica 83 (6): 508-13, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9676023" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9676023</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_15">Rossi G, Donisi A, Casari S, et al.: The International Prognostic Index can be used as a guide to treatment decisions regarding patients with human immunodeficiency virus-related systemic non-Hodgkin lymphoma. Cancer 86 (11): 2391-7, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10590382" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10590382</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_16">Straus DJ, Huang J, Testa MA, et al.: Prognostic factors in the treatment of human immunodeficiency virus-associated non-Hodgkin's lymphoma: analysis of AIDS Clinical Trials Group protocol 142--low-dose versus standard-dose m-BACOD plus granulocyte-macrophage colony-stimulating factor. National Institute of Allergy and Infectious Diseases. J Clin Oncol 16 (11): 3601-6, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9817281" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9817281</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_17">Hoffmann C, Wolf E, Fätkenheuer G, et al.: Response to highly active antiretroviral therapy strongly predicts outcome in patients with AIDS-related lymphoma. AIDS 17 (10): 1521-9, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12824790" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12824790</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_18">Spina M, Vaccher E, Nasti G, et al.: Human immunodeficiency virus-associated Hodgkin's disease. Semin Oncol 27 (4): 480-8, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10950375" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10950375</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_19">Thompson LD, Fisher SI, Chu WS, et al.: HIV-associated Hodgkin lymphoma: a clinicopathologic and immunophenotypic study of 45 cases. Am J Clin Pathol 121 (5): 727-38, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15151213" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15151213</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_20">Hessol NA, Katz MH, Liu JY, et al.: Increased incidence of Hodgkin disease in homosexual men with HIV infection. Ann Intern Med 117 (4): 309-11, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1637026" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1637026</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_21">Re A, Casari S, Cattaneo C, et al.: Hodgkin disease developing in patients infected by human immunodeficiency virus results in clinical features and a prognosis similar to those in patients with human immunodeficiency virus-related non-Hodgkin lymphoma. Cancer 92 (11): 2739-45, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11753946" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11753946</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_22">Dolcetti R, Boiocchi M, Gloghini A, et al.: Pathogenetic and histogenetic features of HIV-associated Hodgkin's disease. Eur J Cancer 37 (10): 1276-87, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11423259" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11423259</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_1_23">Hentrich M, Maretta L, Chow KU, et al.: Highly active antiretroviral therapy (HAART) improves survival in HIV-associated Hodgkin's disease: results of a multicenter study. Ann Oncol 17 (6): 914-9, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16565210" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16565210</span></a>]</div></li></ol></div></div><div id="CDR0000062940__10"><h2 id="_CDR0000062940__10_">Cellular Classification of AIDS-Related Lymphoma</h2><p id="CDR0000062940__11">Pathologically, AIDS-related lymphomas are comprised of a narrow spectrum of
|
|
histologic types consisting almost exclusively of B-cell tumors of aggressive
|
|
type. These include the following:
|
|
</p><ul id="CDR0000062940__50"><li class="half_rhythm"><div> Diffuse large B-cell lymphoma.</div></li><li class="half_rhythm"><div> B-cell immunoblastic lymphoma.</div></li><li class="half_rhythm"><div>Small
|
|
noncleaved lymphoma, either Burkitt or Burkitt-like.</div></li></ul><p id="CDR0000062940__51"> All three pathologic types are
|
|
equally distributed and represent aggressive disease.</p><p id="CDR0000062940__12">AIDS-related lymphomas, though usually of B-cell origin as demonstrated by
|
|
immunoglobulin heavy-chain gene rearrangement studies, have also been shown to
|
|
be oligoclonal and polyclonal as well as monoclonal in origin. Although human immunodeficiency virus (HIV)
|
|
does not appear to have a direct etiologic role, HIV infection does lead to an
|
|
altered immunologic milieu. HIV generally infects T lymphocytes whose loss of
|
|
regulation function leads to hypergammaglobulinemia and polyclonal B-cell
|
|
hyperplasia. B cells are not the targets of HIV infection. Instead,
|
|
Epstein-Barr virus (EBV) is thought to be at least a cofactor in the etiology
|
|
of some of these lymphomas. The EBV genome has been detected in varying
|
|
numbers of patients with AIDS-related lymphomas; molecular analysis suggests
|
|
that the cells were infected before clonal proliferation began.[<a class="bk_pop" href="#CDR0000062940_rl_10_1">1</a>] EBV is
|
|
detected in 30% of patients with small, noncleaved lymphomas and in 80% of patients with
|
|
diffuse, large cell lymphomas. The rare, primary effusion lymphoma consistently
|
|
harbors human herpes virus type-8 and frequently contains EBV.[<a class="bk_pop" href="#CDR0000062940_rl_10_2">2</a>] HIV-related T-cell
|
|
lymphomas have also been identified and appear to be associated with EBV
|
|
infection.[<a class="bk_pop" href="#CDR0000062940_rl_10_3">3</a>]
|
|
</p><div id="CDR0000062940_rl_10"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062940_rl_10_1">Thorley-Lawson DA, Gross A: Persistence of the Epstein-Barr virus and the origins of associated lymphomas. N Engl J Med 350 (13): 1328-37, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15044644" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15044644</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_10_2">Simonelli C, Spina M, Cinelli R, et al.: Clinical features and outcome of primary effusion lymphoma in HIV-infected patients: a single-institution study. J Clin Oncol 21 (21): 3948-54, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/14581418" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14581418</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_10_3">Thomas JA, Cotter F, Hanby AM, et al.: Epstein-Barr virus-related oral T-cell lymphoma associated with human immunodeficiency virus immunosuppression. Blood 81 (12): 3350-6, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8389615" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8389615</span></a>]</div></li></ol></div></div><div id="CDR0000062940__13"><h2 id="_CDR0000062940__13_">Stage Information for AIDS-Related Lymphoma</h2><p id="CDR0000062940__14">Although stage is important in selecting the treatment of patients with
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non-Hodgkin lymphoma (NHL) who do not have AIDS, the majority of patients with AIDS-related lymphomas have far-advanced
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disease. </p><div id="CDR0000062940__15"><h3>Staging Subclassification System</h3><div id="CDR0000062940__139" class="table"><h3><span class="title">Table 1. Anatomic Stage/Prognostic Groups<sup>a</sup></span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65743.1/table/CDR0000062940__139/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062940__139_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;">Prognostic Groups</th></tr></thead><tbody><tr><td colspan="1" rowspan="3" 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></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">OR</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) (rare in Hodgkin lymphoma).</td></tr><tr><td colspan="1" rowspan="3" style="text-align:center;vertical-align:top;"> II</td><td colspan="1" rowspan="1" style="vertical-align:top;">Involvement of two or more lymph node regions on the same side of the diaphragm (II).</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">OR</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). The number of regions involved may be indicated by a subscript Arabic numeral, for example, II<sub>3</sub></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, IIIS). Splenic involvement is designated by the letter S.</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></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">OR</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). Stage IV 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></dl></div></div></div><p id="CDR0000062940__16">The Ann Arbor staging system is commonly used for patients with NHL.[<a class="bk_pop" href="#CDR0000062940_rl_13_1">1</a>,<a class="bk_pop" href="#CDR0000062940_rl_13_2">2</a>] In this system, stage I, II, III, and IV NHL can be subclassified into A and
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B categories: B for those with well-defined generalized symptoms and A for
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those without. The B designation is given to patients with any of the
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following symptoms:
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</p><ul id="CDR0000062940__17"><li class="half_rhythm"><div>Unexplained loss of more than 10% of body weight in the 6 months before
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|
diagnosis.
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</div></li><li class="half_rhythm"><div>Unexplained fever with temperatures higher than 38° C.
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</div></li><li class="half_rhythm"><div>Drenching night sweats. (Refer to the PDQ summary on <a href="/books/n/pdqcis/CDR0000062742/">Hot Flashes and Night Sweats</a> for more information.)
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</div></li></ul><p id="CDR0000062940__140">Occasionally, specialized staging systems are used. The physician should be
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|
aware of the system used in a specific report.</p><p id="CDR0000062940__141">The E designation is used when extranodal lymphoid malignancies arise in
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|
tissues separate from, but near, the major lymphatic aggregates. Stage IV
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|
refers to disease that is diffusely spread throughout an extranodal site, such
|
|
as the liver. If pathologic proof of involvement of one or more extralymphatic
|
|
sites has been documented, the symbol for the site of involvement, followed by
|
|
a plus sign (+), is listed.</p><div id="CDR0000062940__45" class="table"><h3><span class="title">Table 2. Notation for Identification of Sites</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65743.1/table/CDR0000062940__45/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062940__45_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 = 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><p id="CDR0000062940__142">Current practice assigns a clinical stage (CS) based on the findings of the
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|
clinical evaluation and a pathologic stage (PS) based on the findings made as a
|
|
result of invasive procedures beyond the initial biopsy.
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|
</p><p id="CDR0000062940__143">For example, on percutaneous biopsy, a patient with inguinal adenopathy and a
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|
positive lymphangiogram without systemic symptoms might be found to have
|
|
involvement of the liver and bone marrow. The precise stage of such a patient
|
|
would be CS IIA, PS IVA(H+)(M+).
|
|
</p><p id="CDR0000062940__144">A number of other factors that are not included in the above staging system are
|
|
important for the staging and prognosis of patients with NHL. These factors
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|
include the following:</p><ul id="CDR0000062940__145"><li class="half_rhythm"><div>Age.</div></li><li class="half_rhythm"><div>Performance status (PS).</div></li><li class="half_rhythm"><div>Tumor size.</div></li><li class="half_rhythm"><div>Lactate dehydrogenase (LDH) values.</div></li><li class="half_rhythm"><div>The number of extranodal sites.</div></li></ul><p id="CDR0000062940__146">To identify subgroups of patients most
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|
likely to relapse, an international prognostic index was compiled for 2,031 patients with
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|
aggressive NHL.[<a class="bk_pop" href="#CDR0000062940_rl_13_3">3</a>] After validation by several cancer centers (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=65935" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCT00003150</a>),[<a class="bk_pop" href="#CDR0000062940_rl_13_4">4</a>,<a class="bk_pop" href="#CDR0000062940_rl_13_5">5</a>] the major
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|
cooperative groups used this index in the design of new clinical trials.
|
|
The model has been simple to apply, reproducible, and has predicted outcome even after
|
|
patients have achieved a complete remission. The model has identified five
|
|
significant risk factors prognostic of overall survival (OS): age (<60 years vs.
|
|
>60 years), serum LDH (normal vs. elevated), PS (0 or 1
|
|
vs. 2–4), stage (stage I or stage II vs. stage III or stage IV), and extranodal site involvement
|
|
(0 or 1 vs. 2–4). </p><p id="CDR0000062940__147">Patients with two or more risk factors were shown to have a less than 50%
|
|
chance of relapse-free and OS at 5 years. This study also
|
|
identified patients at high risk of relapse based on specific sites of
|
|
involvement, including bone marrow, central nervous system, liver, lung, and
|
|
spleen. Patients at high risk of relapse may benefit from consolidation
|
|
therapy or other approaches under clinical evaluation.[<a class="bk_pop" href="#CDR0000062940_rl_13_3">3</a>]
|
|
Molecular profiles of gene expression using DNA microarrays may help to stratify patients in the future for therapies directed at specific targets and to better predict survival after standard chemotherapy.[<a class="bk_pop" href="#CDR0000062940_rl_13_6">6</a>,<a class="bk_pop" href="#CDR0000062940_rl_13_7">7</a>]</p></div><div id="CDR0000062940_rl_13"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062940_rl_13_1">Lymphoid neoplasms. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 599-628.</div></li><li><div class="bk_ref" id="CDR0000062940_rl_13_2">National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin's Lymphoma Pathologic Classification Project. Cancer 49 (10): 2112-35, 1982. [<a href="https://pubmed.ncbi.nlm.nih.gov/6896167" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6896167</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_13_3">A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med 329 (14): 987-94, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8141877" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8141877</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_13_4">Salles G, de Jong D, Xie W, et al.: Prognostic significance of immunohistochemical biomarkers in diffuse large B-cell lymphoma: a study from the Lunenburg Lymphoma Biomarker Consortium. Blood 117 (26): 7070-8, 2011. [<a href="https://pubmed.ncbi.nlm.nih.gov/21536860" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21536860</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_13_5">Advani RH, Chen H, Habermann TM, et al.: Comparison of conventional prognostic indices in patients older than 60 years with diffuse large B-cell lymphoma treated with R-CHOP in the US Intergroup Study (ECOG 4494, CALGB 9793): consideration of age greater than 70 years in an elderly prognostic index (E-IPI). Br J Haematol 151 (2): 143-51, 2010. [<a href="/pmc/articles/PMC3615251/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3615251</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20735398" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20735398</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_13_6">Rosenwald A, Wright G, Chan WC, et al.: The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346 (25): 1937-47, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/12075054" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12075054</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_13_7">Abramson JS, Shipp MA: Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach. Blood 106 (4): 1164-74, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/15855278" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15855278</span></a>]</div></li></ol></div></div><div id="CDR0000062940__30"><h2 id="_CDR0000062940__30_">Treatment Option Overview for AIDS-Related Lymphoma</h2><p id="CDR0000062940__32">The treatment of patients with AIDS-related lymphomas presents the challenge of integrating therapy
|
|
appropriate for the stage and histologic subset of malignant lymphoma with the
|
|
limitations imposed by HIV infection, which to date is a chronic incurable illness.[<a class="bk_pop" href="#CDR0000062940_rl_30_1">1</a>] In
|
|
addition to antitumor therapy, essential components of an optimal non-Hodgkin
|
|
lymphoma treatment strategy include the following:[<a class="bk_pop" href="#CDR0000062940_rl_30_2">2</a>]
|
|
</p><ul id="CDR0000062940__127"><li class="half_rhythm"><div>Highly active antiretroviral therapy.</div></li><li class="half_rhythm"><div>Prophylaxis for
|
|
opportunistic infections.</div></li><li class="half_rhythm"><div>Rapid recognition and treatment of intercurrent
|
|
infections.</div></li></ul><p id="CDR0000062940__128">Patients with HIV positivity and underlying immunodeficiency
|
|
have poor bone marrow reserve, which compromises the potential for drug dose
|
|
intensity. Intercurrent opportunistic infection is a risk that may
|
|
also lead to a decrease in drug delivery. Furthermore, chemotherapy itself
|
|
compromises the immune system and increases the likelihood of opportunistic
|
|
infection.</p><div id="CDR0000062940_rl_30"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062940_rl_30_1">Levine AM: Acquired immunodeficiency syndrome-related lymphoma: clinical aspects. Semin Oncol 27 (4): 442-53, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/10950371" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10950371</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_30_2">Tirelli U, Bernardi D: Impact of HAART on the clinical management of AIDS-related cancers. Eur J Cancer 37 (10): 1320-4, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11423264" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11423264</span></a>]</div></li></ol></div></div><div id="CDR0000062940__35"><h2 id="_CDR0000062940__35_">AIDS-Related Peripheral/Systemic Lymphoma</h2><p id="CDR0000062940__36">The treatment of AIDS-related lymphomas involves overcoming several problems. These are all
|
|
aggressive lymphomas, which by definition are diffuse large cell/immunoblastic
|
|
lymphoma or small noncleaved cell lymphoma. These lymphomas frequently involve
|
|
the bone marrow and central nervous system (CNS) and, therefore, are usually in an
|
|
advanced stage. In addition, the immunodeficiency of AIDS and the leukopenia
|
|
that is commonly seen with human immunodeficiency virus (HIV) infection makes the use of immunosuppressive
|
|
chemotherapy difficult.
|
|
</p><p id="CDR0000062940__37">A large number of retrospective studies and several prospective studies have
|
|
been reported using regimens such as cyclophosphamide,
|
|
doxorubicin, vincristine, and prednisone (CHOP), methotrexate, bleomycin, doxorubicin, cyclophosphamide,
|
|
vincristine, and dexamethasone (m-BACOD), and infusional cyclophosphamide, doxorubicin, and etoposide.[<a class="bk_pop" href="#CDR0000062940_rl_35_1">1</a>-<a class="bk_pop" href="#CDR0000062940_rl_35_4">4</a>] The patients
|
|
who go into remission are more likely to have less disease, no bone marrow or
|
|
CNS involvement, no prior AIDS-defining illness, and a
|
|
better performance status. Patients at risk for subsequent CNS involvement
|
|
include those with bone marrow involvement or those with Epstein-Barr virus
|
|
identified in the primary tumor or in the cerebrospinal fluid (i.e., by polymerase
|
|
chain reaction).[<a class="bk_pop" href="#CDR0000062940_rl_35_5">5</a>-<a class="bk_pop" href="#CDR0000062940_rl_35_7">7</a>] Intrathecal chemotherapy is usually considered for those
|
|
patients at higher risk for CNS involvement.
|
|
</p><p id="CDR0000062940__88">Before the highly active, antiretroviral-therapy (HAART) era, a randomized trial of patients with HIV and either Burkitt lymphoma (BL) or diffuse large B-cell lymphoma (DLBCL) compared standard dose chemotherapy and growth factor support with reduced-dose chemotherapy.[<a class="bk_pop" href="#CDR0000062940_rl_35_1">1</a>] No difference was found in overall survival (OS) between the two dose levels, and no difference was observed between the historic groups (BL and DLBCL); however, the median survival was equally poor at 6 to 7 months.[<a class="bk_pop" href="#CDR0000062940_rl_35_1">1</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] The introduction of HAART has led to a marked reduction in opportunistic infections, prolonged survival with HIV infection, and a median OS for patients with AIDS-related lymphoma, which is comparable to the outcome in the nonimmunosuppressed population.[<a class="bk_pop" href="#CDR0000062940_rl_35_4">4</a>,<a class="bk_pop" href="#CDR0000062940_rl_35_8">8</a>-<a class="bk_pop" href="#CDR0000062940_rl_35_14">14</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>] The use of HAART has also allowed the use of standard dose and even intensive chemotherapy regimens to be given with reasonable safety to patients with AIDS-related lymphomas, which is comparable to the outcome in non-HIV patients.[<a class="bk_pop" href="#CDR0000062940_rl_35_3">3</a>,<a class="bk_pop" href="#CDR0000062940_rl_35_4">4</a>,<a class="bk_pop" href="#CDR0000062940_rl_35_13">13</a>-<a class="bk_pop" href="#CDR0000062940_rl_35_16">16</a>] </p><p id="CDR0000062940__129">In a retrospective review of 363 patients with HIV-associated lymphoma, survival of patients with HIV-DLBCL improved in the HAART era, but survival of similarly treated patients with HIV-BL remained poor.[<a class="bk_pop" href="#CDR0000062940_rl_35_17">17</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>] Future studies will evaluate if more intensive chemotherapy appropriate for non-HIV patients with BL results in better outcomes for patients with HIV-BL.[<a class="bk_pop" href="#CDR0000062940_rl_35_17">17</a>] A prospective randomized comparison (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=66666" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">AMC-010</a>) of rituximab plus CHOP (R-CHOP) versus CHOP in 150 patients with HIV-DLBCL and HIV-BL showed no difference in OS; treatment-related infectious deaths occurred in 14% of patients who received R-CHOP versus 2% of patients who received CHOP alone (<i>P</i> = .035).[<a class="bk_pop" href="#CDR0000062940_rl_35_18">18</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335125/" class="def">Level of evidence: 1iiA</a>] A Cochrane meta-analysis published in 2009 evaluated 857 patients in four randomized clinical trials; no clinical conclusions regarding the optimal regimen could be reached as a result of varying interventions and the lack of adequately powered trials with a low risk of bias.[<a class="bk_pop" href="#CDR0000062940_rl_35_19">19</a>]</p><p id="CDR0000062940__66">Highly selected patients with resistant or relapsed lymphoma after first-line chemotherapy and with continued responsiveness to HAART underwent second-line chemotherapy followed by high-dose therapy and autologous peripheral stem cell transplantation. Long-term survivors have been reported anecdotally for these highly selected patients who relapsed.[<a class="bk_pop" href="#CDR0000062940_rl_35_20">20</a>-<a class="bk_pop" href="#CDR0000062940_rl_35_23">23</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>]</p><div id="CDR0000062940__TrialSearch_35_sid_5"><h3>Current Clinical Trials</h3><p id="CDR0000062940__TrialSearch_35_10">Check the list of NCI-supported cancer clinical trials that are now accepting patients with
|
|
<a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=41629&tt=1&format=2&cn=1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">AIDS-related peripheral/systemic lymphoma</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062940__TrialSearch_35_18">General information about clinical trials is also available from the <a href="http://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div><div id="CDR0000062940_rl_35"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062940_rl_35_1">Kaplan LD, Straus DJ, Testa MA, et al.: Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med 336 (23): 1641-8, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9171066" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9171066</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_2">Sparano JA, Lee S, Chen MG, et al.: Phase II trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with HIV-associated non-Hodgkin's lymphoma: an Eastern Cooperative Oncology Group Trial (E1494). J Clin Oncol 22 (8): 1491-500, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15084622" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15084622</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_3">Ratner L, Lee J, Tang S, et al.: Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy. J Clin Oncol 19 (8): 2171-8, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11304769" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11304769</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_4">Levine AM, Tulpule A, Espina B, et al.: Liposome-encapsulated doxorubicin in combination with standard agents (cyclophosphamide, vincristine, prednisone) in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma: results of therapy and correlates of response. J Clin Oncol 22 (13): 2662-70, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15226333" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15226333</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_5">Gill PS, Levine AM, Krailo M, et al.: AIDS-related malignant lymphoma: results of prospective treatment trials. J Clin Oncol 5 (9): 1322-8, 1987. [<a href="https://pubmed.ncbi.nlm.nih.gov/2442321" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2442321</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_6">Cingolani A, Gastaldi R, Fassone L, et al.: Epstein-Barr virus infection is predictive of CNS involvement in systemic AIDS-related non-Hodgkin's lymphomas. J Clin Oncol 18 (19): 3325-30, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/11013271" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11013271</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_7">Scadden DT: Epstein-Barr virus, the CNS, and AIDS-related lymphomas: as close as flame to smoke. J Clin Oncol 18 (19): 3323-4, 2000. [<a href="https://pubmed.ncbi.nlm.nih.gov/11013270" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11013270</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_8">Palella FJ Jr, Delaney KM, Moorman AC, et al.: Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 338 (13): 853-60, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9516219" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9516219</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_9">Antinori A, Cingolani A, Alba L, et al.: Better response to chemotherapy and prolonged survival in AIDS-related lymphomas responding to highly active antiretroviral therapy. AIDS 15 (12): 1483-91, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11504980" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11504980</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_10">Hoffmann C, Wolf E, Fätkenheuer G, et al.: Response to highly active antiretroviral therapy strongly predicts outcome in patients with AIDS-related lymphoma. AIDS 17 (10): 1521-9, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12824790" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12824790</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_11">Tam HK, Zhang ZF, Jacobson LP, et al.: Effect of highly active antiretroviral therapy on survival among HIV-infected men with Kaposi sarcoma or non-Hodgkin lymphoma. Int J Cancer 98 (6): 916-22, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11948473" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11948473</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_12">Vaccher E, Spina M, Talamini R, et al.: Improvement of systemic human immunodeficiency virus-related non-Hodgkin lymphoma outcome in the era of highly active antiretroviral therapy. Clin Infect Dis 37 (11): 1556-64, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/14614680" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14614680</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_13">Mounier N, Spina M, Gabarre J, et al.: AIDS-related non-Hodgkin lymphoma: final analysis of 485 patients treated with risk-adapted intensive chemotherapy. Blood 107 (10): 3832-40, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16410446" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16410446</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_14">Weiss R, Mitrou P, Arasteh K, et al.: Acquired immunodeficiency syndrome-related lymphoma: simultaneous treatment with combined cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy and highly active antiretroviral therapy is safe and improves survival--results of the German Multicenter Trial. Cancer 106 (7): 1560-8, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16502436" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16502436</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_15">Wang ES, Straus DJ, Teruya-Feldstein J, et al.: Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer 98 (6): 1196-205, 2003. [<a href="https://pubmed.ncbi.nlm.nih.gov/12973843" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12973843</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_16">Cortes J, Thomas D, Rios A, et al.: Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma/leukemia. Cancer 94 (5): 1492-9, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/11920506" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11920506</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_17">Lim ST, Karim R, Nathwani BN, et al.: AIDS-related Burkitt's lymphoma versus diffuse large-cell lymphoma in the pre-highly active antiretroviral therapy (HAART) and HAART eras: significant differences in survival with standard chemotherapy. J Clin Oncol 23 (19): 4430-8, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/15883411" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15883411</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_18">Kaplan LD, Lee JY, Ambinder RF, et al.: Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood 106 (5): 1538-43, 2005. [<a href="/pmc/articles/PMC1895225/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1895225</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15914552" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15914552</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_19">Martí-Carvajal AJ, Cardona AF, Lawrence A: Interventions for previously untreated patients with AIDS-associated non-Hodgkin's lymphoma. Cochrane Database Syst Rev (3): CD005419, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19588373" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19588373</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_20">Re A, Michieli M, Casari S, et al.: High-dose therapy and autologous peripheral blood stem cell transplantation as salvage treatment for AIDS-related lymphoma: long-term results of the Italian Cooperative Group on AIDS and Tumors (GICAT) study with analysis of prognostic factors. Blood 114 (7): 1306-13, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19451551" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19451551</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_21">Krishnan A, Molina A, Zaia J, et al.: Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas. Blood 105 (2): 874-8, 2005. [<a href="https://pubmed.ncbi.nlm.nih.gov/15388574" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15388574</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_22">Costello RT, Zerazhi H, Charbonnier A, et al.: Intensive sequential chemotherapy with hematopoietic growth factor support for non-Hodgkin lymphoma in patients infected with the human immunodeficiency virus. Cancer 100 (4): 667-76, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/14770420" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14770420</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_35_23">Balsalobre P, Díez-Martín JL, Re A, et al.: Autologous stem-cell transplantation in patients with HIV-related lymphoma. J Clin Oncol 27 (13): 2192-8, 2009. [<a href="https://pubmed.ncbi.nlm.nih.gov/19332732" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19332732</span></a>]</div></li></ol></div></div><div id="CDR0000062940__40"><h2 id="_CDR0000062940__40_">AIDS-Related Primary Central Nervous System Lymphoma (PCNSL)</h2><p id="CDR0000062940__41">Until the 1980s, primary central nervous system lymphoma (PCNSL) was a rare
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disease. PCNSL has increased dramatically in
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association with AIDS.[<a class="bk_pop" href="#CDR0000062940_rl_40_1">1</a>] PCNSL accounts for approximately 0.6% of initial AIDS diagnoses and is the
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second most frequent central nervous system (CNS) mass lesion in adults with AIDS. As with other
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AIDS-related lymphomas, these are usually aggressive B-cell neoplasms, either
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diffuse large cell or diffuse immunoblastic non-Hodgkin lymphoma. Unlike AIDS-related systemic lymphomas, in which 30% to 50% of tumors are
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associated with Epstein-Barr virus (EBV), AIDS-related PCNSL has
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been reported to have a 100% association with EBV.[<a class="bk_pop" href="#CDR0000062940_rl_40_2">2</a>] This percentage
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indicates a pathogenetic role for EBV in this disease. These patients usually
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have evidence of far-advanced AIDS, are severely debilitated, and present with
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focal neurologic symptoms such as seizures, changes in mental status, and
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paralysis.
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</p><p id="CDR0000062940__42">Computed tomographic scans show contrast-enhancing mass lesions that may not
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always be distinguished from other CNS diseases, such as toxoplasmosis, that
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occur in AIDS patients.[<a class="bk_pop" href="#CDR0000062940_rl_40_3">3</a>] Magnetic resonance imaging studies using gadolinium
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contrast may be a more useful initial diagnostic tool in differentiating
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lymphoma from cerebral toxoplasmosis or progressive multifocal
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leukoencephalopathy. Lymphoma tends to present with large lesions, which are
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enhanced by gadolinium. In cerebral toxoplasmosis, ring enhancement is very
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common, lesions tend to be smaller, and multiple lesions are seen.[<a class="bk_pop" href="#CDR0000062940_rl_40_4">4</a>-<a class="bk_pop" href="#CDR0000062940_rl_40_6">6</a>] Use of
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positron emission scanning has demonstrated an improved ability to distinguish
|
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PCNSL from toxoplasmosis.[<a class="bk_pop" href="#CDR0000062940_rl_40_7">7</a>,<a class="bk_pop" href="#CDR0000062940_rl_40_8">8</a>] </p><p id="CDR0000062940__131">PSNCL
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has an increased uptake while toxoplasmosis lesions are metabolically inactive.
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Antibodies against toxoplasmosis may also be very useful because the vast
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majority of cerebral toxoplasmosis occur as a consequence of reactivity of a
|
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previous infection. If the IgG titer is less than 1:4, the disease is unlikely
|
|
to be toxoplasmotic. A lumbar puncture may be useful to detect as many as 23%
|
|
of patients with malignant cells in their cerebrospinal fluid (CSF).
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Evaluating the CSF for EBV DNA may be a useful lymphoma-specific tool since EBV
|
|
is present in all patients with PCNSL. Despite all of these evaluations,
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however, the majority of patients with PCNSL require a pathologic
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diagnosis.[<a class="bk_pop" href="#CDR0000062940_rl_40_9">9</a>-<a class="bk_pop" href="#CDR0000062940_rl_40_11">11</a>] Diagnosis is made by biopsy. Sometimes, a biopsy is
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attempted only after failure of antibiotics for toxoplasmosis, which will
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produce clinical and radiographic improvement within 1 to 3 weeks in patients
|
|
with cerebral toxoplasmosis.[<a class="bk_pop" href="#CDR0000062940_rl_40_12">12</a>] PCNSL is often identified as a
|
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terminal manifestation of AIDS or on postmortem examination.</p><p id="CDR0000062940__43">Radiation therapy alone has usually been used in this group of patients. With
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doses in the 35 Gy to 40 Gy range, median duration of survival has been only
|
|
72 to 119 days.[<a class="bk_pop" href="#CDR0000062940_rl_40_3">3</a>,<a class="bk_pop" href="#CDR0000062940_rl_40_13">13</a>,<a class="bk_pop" href="#CDR0000062940_rl_40_14">14</a>] Survival is longer in younger patients with better
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performance status and the absence of opportunistic infection.[<a class="bk_pop" href="#CDR0000062940_rl_40_15">15</a>] Most patients
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|
respond to treatment by showing partial improvement in neurologic symptoms.
|
|
Autopsies have revealed that these patients die of opportunistic infections as
|
|
well as tumor progression. Treatment of these patients is also complicated by
|
|
other AIDS-related CNS infections, including subacute AIDS encephalitis,
|
|
cytomegalovirus encephalitis, and toxoplasmosis encephalitis. Spontaneous
|
|
remissions have been reported after highly active antiretroviral therapy.[<a class="bk_pop" href="#CDR0000062940_rl_40_16">16</a>]
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</p><div id="CDR0000062940__TrialSearch_40_sid_6"><h3>Current Clinical Trials</h3><p id="CDR0000062940__TrialSearch_40_10">Check the list of NCI-supported cancer clinical trials that are now accepting patients with
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|
<a href="http://www.cancer.gov/search/ClinicalTrialsLink.aspx?Diagnosis=41630&tt=1&format=2&cn=1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">AIDS-related primary CNS lymphoma</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062940__TrialSearch_40_18">General information about clinical trials is also available from the <a href="http://www.cancer.gov/about-cancer/treatment/clinical-trials" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NCI website</a>.</p></div><div id="CDR0000062940_rl_40"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062940_rl_40_1">Ziegler JL, Beckstead JA, Volberding PA, et al.: Non-Hodgkin's lymphoma in 90 homosexual men. Relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome. N Engl J Med 311 (9): 565-70, 1984. [<a href="https://pubmed.ncbi.nlm.nih.gov/6611504" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6611504</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_2">MacMahon EM, Glass JD, Hayward SD, et al.: Epstein-Barr virus in AIDS-related primary central nervous system lymphoma. Lancet 338 (8773): 969-73, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1681341" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1681341</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_3">Goldstein JD, Dickson DW, Moser FG, et al.: Primary central nervous system lymphoma in acquired immune deficiency syndrome. A clinical and pathologic study with results of treatment with radiation. Cancer 67 (11): 2756-65, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/2025839" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2025839</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_4">Nyberg DA, Federle MP: AIDS-related Kaposi sarcoma and lymphomas. Semin Roentgenol 22 (1): 54-65, 1987. [<a href="https://pubmed.ncbi.nlm.nih.gov/3547679" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3547679</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_5">Fine HA, Mayer RJ: Primary central nervous system lymphoma. Ann Intern Med 119 (11): 1093-104, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8239229" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8239229</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_6">Ciricillo SF, Rosenblum ML: Use of CT and MR imaging to distinguish intracranial lesions and to define the need for biopsy in AIDS patients. J Neurosurg 73 (5): 720-4, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2213162" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2213162</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_7">Hoffman JM, Waskin HA, Schifter T, et al.: FDG-PET in differentiating lymphoma from nonmalignant central nervous system lesions in patients with AIDS. J Nucl Med 34 (4): 567-75, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8455072" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8455072</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_8">Pierce MA, Johnson MD, Maciunas RJ, et al.: Evaluating contrast-enhancing brain lesions in patients with AIDS by using positron emission tomography. Ann Intern Med 123 (8): 594-8, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7677300" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7677300</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_9">Cinque P, Brytting M, Vago L, et al.: Epstein-Barr virus DNA in cerebrospinal fluid from patients with AIDS-related primary lymphoma of the central nervous system. Lancet 342 (8868): 398-401, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8101902" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8101902</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_10">Cingolani A, De Luca A, Larocca LM, et al.: Minimally invasive diagnosis of acquired immunodeficiency syndrome-related primary central nervous system lymphoma. J Natl Cancer Inst 90 (5): 364-9, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9498486" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9498486</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_11">Yarchoan R, Jaffe ES, Little R: Diagnosing central nervous system lymphoma in the setting of AIDS: a step forward. J Natl Cancer Inst 90 (5): 346-7, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9498478" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9498478</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_12">Mathews C, Barba D, Fullerton SC: Early biopsy versus empiric treatment with delayed biopsy of non-responders in suspected HIV-associated cerebral toxoplasmosis: a decision analysis. AIDS 9 (11): 1243-50, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/8561977" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8561977</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_13">Baumgartner JE, Rachlin JR, Beckstead JH, et al.: Primary central nervous system lymphomas: natural history and response to radiation therapy in 55 patients with acquired immunodeficiency syndrome. J Neurosurg 73 (2): 206-11, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2366078" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2366078</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_14">Remick SC, Diamond C, Migliozzi JA, et al.: Primary central nervous system lymphoma in patients with and without the acquired immune deficiency syndrome. A retrospective analysis and review of the literature. Medicine (Baltimore) 69 (6): 345-60, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2233232" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2233232</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_15">Corn BW, Donahue BR, Rosenstock JG, et al.: Performance status and age as independent predictors of survival among AIDS patients with primary CNS lymphoma: a multivariate analysis of a multi-institutional experience. Cancer J Sci Am 3 (1): 52-6, 1997 Jan-Feb. [<a href="https://pubmed.ncbi.nlm.nih.gov/9072309" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9072309</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062940_rl_40_16">McGowan JP, Shah S: Long-term remission of AIDS-related primary central nervous system lymphoma associated with highly active antiretroviral therapy. AIDS 12 (8): 952-4, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9631151" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9631151</span></a>]</div></li></ol></div></div><div id="CDR0000062940__53"><h2 id="_CDR0000062940__53_">Changes to This Summary (04/02/2015)</h2><p id="CDR0000062940__54">The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.</p><p id="CDR0000062940__161">Editorial changes were made to this summary.</p><p id="CDR0000062940__disclaimerHP_3">This summary is written and maintained by the <a href="http://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="#CDR0000062940__AboutThis_1">About This PDQ Summary</a> and <a href="http://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="CDR0000062940__AboutThis_1"><h2 id="_CDR0000062940__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000062940__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000062940__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of AIDS-related 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="CDR0000062940__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000062940__AboutThis_5">This summary is reviewed regularly and updated as necessary by the <a href="http://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="CDR0000062940__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000062940__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="CDR0000062940__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 reviewers for AIDS-Related Lymphoma Treatment are:</p><ul><li class="half_rhythm"><div>Eric J. Seifter, MD (Johns Hopkins University)</div></li><li class="half_rhythm"><div>Minh Tam Truong, MD (Boston University Medical Center)</div></li></ul><p id="CDR0000062940__AboutThis_9">Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's <a href="http://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="CDR0000062940__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000062940__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="CDR0000062940__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000062940__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="CDR0000062940__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000062940__AboutThis_15">National Cancer Institute: PDQ® AIDS-Related Lymphoma Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: <a href="http://www.cancer.gov/types/lymphoma/hp/aids-related-treatment-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">http://www.cancer.gov/types/lymphoma/hp/aids-related-treatment-pdq</a>. Accessed <MM/DD/YYYY>.</p><p id="CDR0000062940__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="http://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="CDR0000062940__AboutThis_17"><h3>Disclaimer</h3><p id="CDR0000062940__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="http://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="CDR0000062940__AboutThis_20"><h3>Contact Us</h3><p id="CDR0000062940__AboutThis_21">More information about contacting us or receiving help with the Cancer.gov website can be found on our <a href="http://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="http://www.cancer.gov/contact/email-us" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Email Us</a>.</p></div></div><div id="CDR0000062940__GetMore_3"><h2 id="_CDR0000062940__GetMore_3_">Get More Information From NCI</h2><p id="CDR0000062940__GetMore_15"><i><b>Call 1-800-4-CANCER</b></i></p><p id="CDR0000062940__GetMore_16">For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 a.m. to 8:00 p.m., Eastern Time. A trained Cancer Information Specialist is available to answer your questions.</p><p id="CDR0000062940__GetMore_25"><i><b>Chat online
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<div class="post-content"><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div><div class="small"><span class="label">Bookshelf ID: NBK65743</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/26389186" title="PubMed record of this page" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">26389186</a></span></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/NBK65743.1/?report=reader">PubReader</a></li><li><a href="/books/NBK65743.1/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK65743" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK65743" style="display:none" title="Cite this Page"><div class="bk_tt">PDQ Adult Treatment Editorial Board. AIDS-Related Lymphoma Treatment (PDQ®): Health Professional Version. 2015 Apr 2. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. <span class="bk_cite_avail"></span></div></div></li><li><a href="#" class="toggle-glossary-link" title="Enable/disable links to the glossary">Disable Glossary Links</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Version History</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter shutter_closed" title="Show/hide content" remembercollapsed="true" pgsec_name="version_history" id="Shutter"></a></div><div class="portlet_content" style="display: none;"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><span class="bk_col_itm"><a href="/books/NBK65743.10/">NBK65743.10</a></span> September 18, 2024</li><li><span class="bk_col_itm"><a href="/books/NBK65743.9/">NBK65743.9</a></span> September 30, 2022</li><li><span class="bk_col_itm"><a href="/books/NBK65743.8/">NBK65743.8</a></span> October 8, 2020</li><li><span class="bk_col_itm"><a href="/books/NBK65743.7/">NBK65743.7</a></span> June 27, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65743.6/">NBK65743.6</a></span> January 25, 2019</li><li><span class="bk_col_itm"><a href="/books/NBK65743.5/">NBK65743.5</a></span> August 8, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK65743.4/">NBK65743.4</a></span> July 27, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK65743.3/">NBK65743.3</a></span> February 4, 2018</li><li><span class="bk_col_itm"><a href="/books/NBK65743.2/">NBK65743.2</a></span> October 2, 2015</li><li><span class="bk_col_itm">NBK65743.1</span> April 2, 2015 (Displayed Version)</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="#CDR0000062940__1" ref="log$=inpage&link_id=inpage">General Information About AIDS-Related Lymphoma</a></li><li><a href="#CDR0000062940__10" ref="log$=inpage&link_id=inpage">Cellular Classification of AIDS-Related Lymphoma</a></li><li><a href="#CDR0000062940__13" ref="log$=inpage&link_id=inpage">Stage Information for AIDS-Related Lymphoma</a></li><li><a href="#CDR0000062940__30" ref="log$=inpage&link_id=inpage">Treatment Option Overview for AIDS-Related Lymphoma</a></li><li><a href="#CDR0000062940__35" ref="log$=inpage&link_id=inpage">AIDS-Related Peripheral/Systemic Lymphoma</a></li><li><a href="#CDR0000062940__40" ref="log$=inpage&link_id=inpage">AIDS-Related Primary Central Nervous System Lymphoma (PCNSL)</a></li><li><a href="#CDR0000062940__53" ref="log$=inpage&link_id=inpage">Changes to This Summary (04/02/2015)</a></li><li><a href="#CDR0000062940__AboutThis_1" ref="log$=inpage&link_id=inpage">About This PDQ Summary</a></li><li><a href="#CDR0000062940__GetMore_3" ref="log$=inpage&link_id=inpage">Get More Information From NCI</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/NBK65920/">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="#" 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