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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="#__NBK65727_dtls__">Show details</a><div style="display:none" class="ui-widget" id="__NBK65727_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="_NBK65727_"><span class="title" itemprop="name">Adult Acute Lymphoblastic Leukemia 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 17, 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="CDR0000062864__248">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of acute lymphoblastic leukemia. 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="CDR0000062864__249">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="CDR0000062864__1"><h2 id="_CDR0000062864__1_">General Information About Adult Acute Lymphoblastic Leukemia (ALL)</h2><p id="CDR0000062864__193">ALL (also called acute lymphocytic leukemia) is an aggressive type of leukemia characterized by the presence of too many lymphoblasts or lymphocytes in the bone marrow and peripheral blood. It can spread to the lymph nodes, spleen, liver, central nervous system (CNS), and other organs. Without treatment, ALL usually progresses quickly.</p><p id="CDR0000062864__194">Signs and symptoms of ALL may include the following:</p><ul id="CDR0000062864__195"><li class="half_rhythm"><div>Weakness or fatigue.</div></li><li class="half_rhythm"><div>Fever or night sweats.</div></li><li class="half_rhythm"><div>Bruises or bleeds easily (i.e., bleeding gums, purplish patches in the skin, or petechiae [flat, pinpoint spots under the skin]).</div></li><li class="half_rhythm"><div>Shortness of breath.</div></li><li class="half_rhythm"><div>Unexpected weight loss or anorexia.</div></li><li class="half_rhythm"><div>Pain in the bones or joints.</div></li><li class="half_rhythm"><div>Swollen lymph nodes, particularly lymph nodes in the neck, armpit, or groin, which are usually painless.</div></li><li class="half_rhythm"><div>Swelling or discomfort in the abdomen.</div></li><li class="half_rhythm"><div>Frequent infections.</div></li></ul><p id="CDR0000062864__196">ALL occurs in both children and adults. It is the most common type of cancer in children, and treatment results in a good chance for a cure. For adults, the prognosis is not as optimistic. This summary discusses ALL in adults. (Refer to the PDQ summary on <a href="/books/n/pdqcis/CDR0000062923/">Childhood Acute Lymphoblastic Leukemia Treatment</a> for more information about ALL in children.) </p><div id="CDR0000062864__14"><h3>Incidence and Mortality</h3><p id="CDR0000062864__228">Estimated new cases and deaths from ALL in the United States in 2015:[<a class="bk_pop" href="#CDR0000062864_rl_1_1">1</a>]</p><ul id="CDR0000062864__16"><li class="half_rhythm"><div>New cases: 6,250.</div></li><li class="half_rhythm"><div>Deaths: 1,450.</div></li></ul></div><div id="CDR0000062864__44"><h3>Anatomy</h3><p id="CDR0000062864__214">ALL presumably arises from malignant transformation of B- or T-cell progenitor cells.[<a class="bk_pop" href="#CDR0000062864_rl_1_2">2</a>] It is more commonly seen in children, but can occur at any age. The disease is characterized by the accumulation of lymphoblasts in the marrow or in various extramedullary sites, frequently accompanied by suppression of normal hematopoiesis. B- and T-cell lymphoblastic leukemia cells express surface antigens that parallel their respective lineage developments. Precursor B-cell ALL cells typically express CD10, CD19, and CD34 on their surface along, with nuclear terminal deoxynucleotide transferase (TdT), while precursor T-cell ALL cells commonly express CD2, CD3, CD7, CD34, and TdT.</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figCDR0000062864199" co-legend-rid="figlgndCDR0000062864199"><a href="/books/NBK65727.1/figure/CDR0000062864__199/?report=objectonly" target="object" title="Figure" class="img_link icnblk_img figpopup" rid-figpopup="figCDR0000062864199" rid-ob="figobCDR0000062864199"><img class="small-thumb" src="/books/NBK65727.1/bin/CDR0000526538.gif" src-large="/books/NBK65727.1/bin/CDR0000526538.jpg" alt="Blood cell development" /></a><div class="icnblk_cntnt" id="figlgndCDR0000062864199"><h4 id="CDR0000062864__199"><a href="/books/NBK65727.1/figure/CDR0000062864__199/?report=objectonly" target="object" rid-ob="figobCDR0000062864199">Figure</a></h4><p class="float-caption no_bottom_margin">Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell. </p></div></div></div><div id="CDR0000062864__20"><h3>Molecular Genetics</h3><p id="CDR0000062864__21">It has been recognized for many years that some patients presenting with acute
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leukemia may have a cytogenetic abnormality that is cytogenetically
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indistinguishable from the Philadelphia chromosome (Ph1).[<a class="bk_pop" href="#CDR0000062864_rl_1_3">3</a>] The Ph1 occurs in only 1% to 2% of patients with acute myeloid leukemia (AML), but it occurs in about 20% of
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adults and a small percentage of children with ALL.[<a class="bk_pop" href="#CDR0000062864_rl_1_4">4</a>] In the majority of
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children and in more than one-half of adults with Ph1-positive
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ALL, the molecular abnormality is different from that in Ph1-positive chronic
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myelogenous leukemia (CML).
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</p><p id="CDR0000062864__22"> Many patients who
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have molecular evidence of the <i>bcr-abl</i> fusion gene, which characterizes the Ph1, have no evidence of the abnormal chromosome by cytogenetics.
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The <i>bcr-abl</i> fusion gene may be detectable only by fluorescence in situ hybridization (FISH) or reverse-transcriptase polymerase chain reaction (RT-PCR) because many patients have a different fusion protein from the one found in
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CML (p190 vs. p210). These tests should be performed, whenever
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possible, in patients with ALL, especially in those with B-cell lineage disease.</p><p id="CDR0000062864__23">L3 ALL is associated with a variety of translocations that
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involve translocation of the <i>c-myc</i> proto-oncogene to the immunoglobulin gene
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locus t(2;8), t(8;12), and t(8;22).</p></div><div id="CDR0000062864__26"><h3>Diagnosis</h3><p id="CDR0000062864__215">Patients with ALL may present with a variety of hematologic derangements ranging from pancytopenia to hyperleukocytosis. In addition to a history and physical, the initial workup should include: </p><ul id="CDR0000062864__216"><li class="half_rhythm"><div>Complete blood count with differential.</div></li><li class="half_rhythm"><div>A chemistry panel (including uric acid, creatinine, blood urea nitrogen, potassium, phosphate, calcium, bilirubin, and hepatic transaminases).</div></li><li class="half_rhythm"><div>Fibrinogen and tests of coagulation as a screen for disseminated intravascular coagulation.</div></li><li class="half_rhythm"><div>A careful screen for evidence of active infection.</div></li></ul><p id="CDR0000062864__217">A bone marrow biopsy and aspirate are routinely performed even in T-cell ALL to determine the extent of marrow involvement. Malignant cells should be sent for conventional cytogenetic studies, as detection of the Ph1 t(9;22), <i>myc</i> gene rearrangements (in Burkitt leukemia), and <i>MLL</i> gene rearrangements add important prognostic information. Flow cytometry should be performed to characterize expression of lineage-defining antigens and allow determination of the specific ALL subtype. In addition, for B-cell disease, the malignant cells should be analyzed using RT-PCR and FISH for evidence of the <i>bcr-abl</i> fusion gene. This last point is of utmost importance, as timely diagnosis of Ph1 ALL will significantly change the therapeutic approach.</p><p id="CDR0000062864__32">Diagnostic
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confusion with AML, hairy cell leukemia, and
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malignant lymphoma is not uncommon. Proper diagnosis is crucial because of the
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difference in prognosis and treatment of ALL and AML. Immunophenotypic
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analysis is essential because leukemias that do not express myeloperoxidase
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include M0 AML, M7 AML, and ALL.
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</p><p id="CDR0000062864__33">The examination of bone marrow
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aspirates and/or biopsy specimens should be done by an experienced oncologist,
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hematologist, hematopathologist, or general pathologist who is capable of
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interpreting conventional and specially stained specimens.</p></div><div id="CDR0000062864__34"><h3>Prognosis and Survival</h3><p id="CDR0000062864__155">Factors associated with prognosis in patients with ALL include the following:</p><ul id="CDR0000062864__156"><li class="half_rhythm"><div class="half_rhythm"><b>Age:</b> Age, which is a significant factor in
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childhood ALL and AML, may be an important prognostic factor in adult
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ALL. In one study, overall, the prognosis was better in patients younger than
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25 years; another study found a better prognosis in patients younger than 35
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years. These findings may, in part, be related to the increased incidence of
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the Ph1 in older ALL patients, a subgroup associated
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with poor prognosis.[<a class="bk_pop" href="#CDR0000062864_rl_1_5">5</a>,<a class="bk_pop" href="#CDR0000062864_rl_1_6">6</a>] </div></li><li class="half_rhythm"><div class="half_rhythm"><b>CNS involvement:</b> As in childhood ALL, adult patients with ALL are at risk of developing CNS involvement during the course of their disease. This is particularly true for patients with L3 (Burkitt) morphology.[<a class="bk_pop" href="#CDR0000062864_rl_1_7">7</a>] Both treatment and
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prognosis are influenced by this complication. </div></li><li class="half_rhythm"><div class="half_rhythm"><b>Cellular morphology:</b> Patients with L3 morphology showed improved outcomes, as evidenced in a completed Cancer and Leukemia Group B study (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=77643" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CLB-9251</a> [<a href="https://clinicaltrials.gov/show/NCT00002494" title="Study NCT00002494" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT00002494</a>]), when treated according to
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specific treatment algorithms.[<a class="bk_pop" href="#CDR0000062864_rl_1_8">8</a>,<a class="bk_pop" href="#CDR0000062864_rl_1_9">9</a>] This study found that L3 leukemia can be cured with aggressive, rapidly cycling lymphoma-like
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chemotherapy regimens.[<a class="bk_pop" href="#CDR0000062864_rl_1_8">8</a>,<a class="bk_pop" href="#CDR0000062864_rl_1_10">10</a>,<a class="bk_pop" href="#CDR0000062864_rl_1_11">11</a>]</div></li><li class="half_rhythm"><div class="half_rhythm"><b>Chromosomal abnormalities:</b> Chromosomal
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abnormalities, including aneuploidy and translocations, have been described and
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may correlate with prognosis.[<a class="bk_pop" href="#CDR0000062864_rl_1_12">12</a>] In particular, patients with Ph1-positive t(9;22) ALL have a
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poor prognosis and represent more than 30% of adult cases. <i>Bcr-abl</i>-rearranged leukemias that do not
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demonstrate the classical Ph1 carry a poor prognosis that is similar
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to those that are Ph1-positive. Patients with Ph1-positive ALL are rarely cured with chemotherapy, although long-term survival is now being routinely reported when such patients are treated with combinations of chemotherapy and <i>Bcr-abl</i> tyrosine kinase inhibitors. </div><div class="half_rhythm">Two other chromosomal abnormalities with poor prognosis are t(4;11), which is characterized by rearrangements of the <i>MLL</i> gene and may be rearranged despite normal cytogenetics, and t(9;22). In addition to t(4;11) and t(9;22), compared with patients with a normal karyotype, patients
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with deletion of chromosome 7 or trisomy 8 have been reported to have a lower
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probability of survival at 5 years.[<a class="bk_pop" href="#CDR0000062864_rl_1_13">13</a>] In a multivariate analysis, karyotype was the most important
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predictor of disease-free survival.[<a class="bk_pop" href="#CDR0000062864_rl_1_13">13</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335148/" class="def">Level of evidence: 3iiDii</a>]</div></li></ul></div><div id="CDR0000062864__42"><h3> Late Effects of Treatment for Adult ALL</h3><p id="CDR0000062864__43">Long-term follow-up of 30 patients with ALL in remission for at least 10 years has demonstrated ten cases of secondary malignancies. Of 31 long-term female survivors of ALL or AML younger than 40 years, 26 resumed normal menstruation following completion of therapy. Among 36 live offspring of survivors, two congenital problems occurred.[<a class="bk_pop" href="#CDR0000062864_rl_1_14">14</a>]</p></div><div id="CDR0000062864__243"><h3>Related Summaries</h3><p id="CDR0000062864__244">Other PDQ summaries containing information related to acute lymphoblastic leukemia include the following:</p><ul id="CDR0000062864__245"><li class="half_rhythm"><div><a href="/books/n/pdqcis/CDR0000062923/">Childhood Acute Lymphoblastic Leukemia Treatment</a></div></li></ul></div><div id="CDR0000062864_rl_1"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062864_rl_1_1">American Cancer Society: Cancer Facts and Figures 2015. Atlanta, Ga: American Cancer Society, 2015. <a href="http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">Available online</a>. Last accessed July 1, 2015.</div></li><li><div class="bk_ref" id="CDR0000062864_rl_1_2">Pui CH, Jeha S: New therapeutic strategies for the treatment of acute lymphoblastic leukaemia. Nat Rev Drug Discov 6 (2): 149-65, 2007. [<a href="https://pubmed.ncbi.nlm.nih.gov/17268486" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17268486</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_1_3">Peterson LC, Bloomfield CD, Brunning RD: Blast crisis as an initial or terminal manifestation of chronic myeloid leukemia: a study of 28 patients. Am J Med 60(2): 209-220, 1976. [<a href="https://pubmed.ncbi.nlm.nih.gov/1062162" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1062162</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_1_4">Secker-Walker LM, Cooke HM, Browett PJ, et al.: Variable Philadelphia breakpoints and potential lineage restriction of bcr rearrangement in acute lymphoblastic leukemia. Blood 72 (2): 784-91, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3165301" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3165301</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_1_5">Gaynor J, Chapman D, Little C, et al.: A cause-specific hazard rate analysis of prognostic factors among 199 adults with acute lymphoblastic leukemia: the Memorial Hospital experience since 1969. J Clin Oncol 6 (6): 1014-30, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3163722" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3163722</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_1_6">Hoelzer D, Thiel E, Löffler H, et al.: Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 71 (1): 123-31, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3422030" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3422030</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_1_7">Kantarjian HM, Walters RS, Smith TL, et al.: Identification of risk groups for development of central nervous system leukemia in adults with acute lymphocytic leukemia. Blood 72 (5): 1784-9, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3052630" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3052630</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_1_8">Lee EJ, Petroni GR, Schiffer CA, et al.: Brief-duration high-intensity chemotherapy for patients with small noncleaved-cell lymphoma or FAB L3 acute lymphocytic leukemia: results of cancer and leukemia group B study 9251. J Clin Oncol 19 (20): 4014-22, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11600602" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11600602</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_1_9">Hoelzer D, Ludwig WD, Thiel E, et al.: Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 87 (2): 495-508, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8555471" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8555471</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_1_10">Fenaux P, Lai JL, Miaux O, et al.: Burkitt cell acute leukaemia (L3 ALL) in adults: a report of 18 cases. Br J Haematol 71 (3): 371-6, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2930722" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2930722</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_1_11">Reiter A, Schrappe M, Ludwig WD, et al.: Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group. Blood 80 (10): 2471-8, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1421370" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1421370</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_1_12">Chromosomal abnormalities and their clinical significance in acute lymphoblastic leukemia. Third International Workshop on Chromosomes in Leukemia. Cancer Res 43 (2): 868-73, 1983. [<a href="https://pubmed.ncbi.nlm.nih.gov/6571719" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6571719</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_1_13">Wetzler M, Dodge RK, Mrózek K, et al.: Prospective karyotype analysis in adult acute lymphoblastic leukemia: the cancer and leukemia Group B experience. Blood 93 (11): 3983-93, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10339508" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10339508</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_1_14">Micallef IN, Rohatiner AZ, Carter M, et al.: Long-term outcome of patients surviving for more than ten years following treatment for acute leukaemia. Br J Haematol 113 (2): 443-5, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11380414" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11380414</span></a>]</div></li></ol></div></div><div id="CDR0000062864__48"><h2 id="_CDR0000062864__48_">Cellular Classification of Adult ALL</h2><p id="CDR0000062864__50">The following leukemic cell characteristics are important: </p><ul id="CDR0000062864__51"><li class="half_rhythm"><div>Morphological features.</div></li><li class="half_rhythm"><div>Cytogenetic characteristics. </div></li><li class="half_rhythm"><div>Immunologic cell surface and biochemical markers. </div></li><li class="half_rhythm"><div>Cytochemistry.</div></li></ul><p id="CDR0000062864__52">In adults, French-American-British (FAB) L1 morphology (more mature-appearing lymphoblasts) is present in fewer than 50% of patients, and L2
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morphology (more immature and pleomorphic) predominates.[<a class="bk_pop" href="#CDR0000062864_rl_48_1">1</a>] L3 (Burkitt) acute lymphoblastic leukemia (ALL) is much less common than the other two FAB subtypes. It is characterized by blasts with cytoplasmic vacuolizations and surface expression of immunoglobulin, and the bone marrow often has an appearance described as a “starry sky” owing to the presence of numerous apoptotic cells. L3 ALL is associated with a variety of translocations that
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involve translocation of the <i>c-myc</i> proto-oncogene to the immunoglobulin gene
|
|
locus t(2;8), t(8;12), and t(8;22).</p><p id="CDR0000062864__163">Some patients presenting with acute
|
|
leukemia may have a cytogenetic abnormality that is morphologically
|
|
indistinguishable from the Philadelphia chromosome (Ph1).[<a class="bk_pop" href="#CDR0000062864_rl_48_2">2</a>] The Ph1 occurs in only 1% to 2% of patients with acute myeloid leukemia (AML), but it occurs in about 20% of
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adults and a small percentage of children with ALL.[<a class="bk_pop" href="#CDR0000062864_rl_48_3">3</a>] In the majority of
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|
children and in more than one-half of adults with Ph1-positive
|
|
ALL, the molecular abnormality is different from that in Ph1-positive chronic
|
|
myelogenous leukemia (CML).
|
|
</p><p id="CDR0000062864__164"> Many patients who
|
|
have molecular evidence of the <i>bcr-abl</i> fusion gene, which characterizes the Ph1, have no evidence of the abnormal chromosome by cytogenetics.
|
|
The <i>bcr-abl</i> fusion gene may be detectable only by pulsed-field gel electrophoresis or reverse-transcriptase polymerase chain reaction for the <i>bcr-abl</i> fusion gene because many patients have a different fusion protein from the one found in
|
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CML (p190 vs. p210). </p><p id="CDR0000062864__54">Using heteroantisera and monoclonal antibodies, ALL cells can be divided into several subtypes (see Table <a class="figpopup" href="/books/NBK65727.1/table/CDR0000062864__222/?report=objectonly" target="object" rid-figpopup="figCDR0000062864222" rid-ob="figobCDR0000062864222">1</a> ).[<a class="bk_pop" href="#CDR0000062864_rl_48_1">1</a>,<a class="bk_pop" href="#CDR0000062864_rl_48_4">4</a>-<a class="bk_pop" href="#CDR0000062864_rl_48_6">6</a>]</p><div id="CDR0000062864__222" class="table"><h3><span class="title">Table 1. Frequency of ALL Cell Subtypes</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65727.1/table/CDR0000062864__222/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062864__222_lrgtbl__"><table class="no_top_margin"><thead><tr><th colspan="1" rowspan="1" style="vertical-align:top;">Cell Subtype</th><th colspan="1" rowspan="1" style="vertical-align:top;">Approximate Frequency</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" style="vertical-align:top;">Early B-cell lineage</td><td colspan="1" rowspan="1" style="vertical-align:top;">80% </td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">T cells</td><td colspan="1" rowspan="1" style="vertical-align:top;">10%–15%</td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;">B cells with surface immunoglobulins</td><td colspan="1" rowspan="1" style="vertical-align:top;"><5%</td></tr></tbody></table></div></div><p id="CDR0000062864__56">About 95% of all types of ALL (except Burkitt, which usually has an L3 morphology by the FAB classification) have elevated terminal deoxynucleotidyl transferase (TdT) expression. This elevation is extremely useful in diagnosis; if concentrations of the enzyme are not elevated, the diagnosis of ALL is suspect. However, 20% of cases of AML may express TdT; therefore, its usefulness as a lineage marker is limited. Because Burkitt leukemias are managed according to different treatment algorithms, it is important to specifically identify these cases prospectively by their L3 morphology, absence of TdT, and expression of surface immunoglobulin. Patients with Burkitt leukemias will typically have one of the following three chromosomal translocations: </p><ul id="CDR0000062864__57"><li class="half_rhythm"><div>t(8;14).</div></li><li class="half_rhythm"><div>t(2;8).</div></li><li class="half_rhythm"><div>t(8;22).</div></li></ul><div id="CDR0000062864_rl_48"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062864_rl_48_1">Brearley RL, Johnson SA, Lister TA: Acute lymphoblastic leukaemia in adults: clinicopathological correlations with the French-American-British (FAB) co-operative group classification. Eur J Cancer 15 (6): 909-14, 1979. [<a href="https://pubmed.ncbi.nlm.nih.gov/291508" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 291508</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_48_2">Peterson LC, Bloomfield CD, Brunning RD: Blast crisis as an initial or terminal manifestation of chronic myeloid leukemia: a study of 28 patients. Am J Med 60(2): 209-220, 1976. [<a href="https://pubmed.ncbi.nlm.nih.gov/1062162" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1062162</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_48_3">Secker-Walker LM, Cooke HM, Browett PJ, et al.: Variable Philadelphia breakpoints and potential lineage restriction of bcr rearrangement in acute lymphoblastic leukemia. Blood 72 (2): 784-91, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3165301" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3165301</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_48_4">Hoelzer D, Thiel E, Löffler H, et al.: Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 71 (1): 123-31, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3422030" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3422030</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_48_5">Sobol RE, Royston I, LeBien TW, et al.: Adult acute lymphoblastic leukemia phenotypes defined by monoclonal antibodies. Blood 65 (3): 730-5, 1985. [<a href="https://pubmed.ncbi.nlm.nih.gov/3855666" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3855666</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_48_6">Foon KA, Billing RJ, Terasaki PI, et al.: Immunologic classification of acute lymphoblastic leukemia. Implications for normal lymphoid differentiation. Blood 56 (6): 1120-6, 1980. [<a href="https://pubmed.ncbi.nlm.nih.gov/6969097" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6969097</span></a>]</div></li></ol></div></div><div id="CDR0000062864__58"><h2 id="_CDR0000062864__58_">Stage Information for Adult ALL</h2><p id="CDR0000062864__59">There is no clear-cut staging system for this disease. This disease is classified as untreated, in remission, or recurrent. </p><div id="CDR0000062864__60"><h3>Untreated Adult ALL</h3><p id="CDR0000062864__61">For a newly diagnosed patient with no prior treatment, untreated adult acute lymphoblastic leukemia (ALL) is defined by the following:</p><ul id="CDR0000062864__62"><li class="half_rhythm"><div>Abnormal white blood cell count
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and differential.</div></li><li class="half_rhythm"><div>Abnormal hematocrit/hemoglobin and platelet counts.</div></li><li class="half_rhythm"><div>Abnormal
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bone marrow with more than 5% blasts.</div></li><li class="half_rhythm"><div>Signs and symptoms of the disease.</div></li></ul></div><div id="CDR0000062864__63"><h3>Adult ALL in Remission</h3><p id="CDR0000062864__64">A patient who has received remission-induction treatment of ALL is in remission if all of the following criteria are met:</p><ul id="CDR0000062864__65"><li class="half_rhythm"><div>Bone marrow is normocellular with no more than 5% blasts.</div></li><li class="half_rhythm"><div>There are no
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signs or symptoms of the disease.</div></li><li class="half_rhythm"><div>There are no signs or symptoms of central nervous
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system leukemia or other extramedullary infiltration.</div></li><li class="half_rhythm"><div>All of the following
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laboratory values are within normal limits:<dl id="CDR0000062864__66" class="temp-labeled-list"><dt>-</dt><dd><p class="no_top_margin">White blood cell count and
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differential.</p></dd><dt>-</dt><dd><p class="no_top_margin">Hematocrit/hemoglobin level.</p></dd><dt>-</dt><dd><p class="no_top_margin">Platelet count.</p></dd></dl></div></li></ul></div></div><div id="CDR0000062864__69"><h2 id="_CDR0000062864__69_">Treatment Option Overview for ALL</h2><p id="CDR0000062864__70">Successful treatment of acute lymphoblastic leukemia (ALL) consists of the
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control of bone marrow and systemic disease and the treatment (or
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prevention) of sanctuary-site disease, particularly the central nervous system
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(CNS).[<a class="bk_pop" href="#CDR0000062864_rl_69_1">1</a>,<a class="bk_pop" href="#CDR0000062864_rl_69_2">2</a>] The cornerstone of this strategy includes systemically
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administered combination chemotherapy with CNS preventive therapy. CNS
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prophylaxis is achieved with chemotherapy (intrathecal and/or high-dose
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systemic therapy) and, in some cases, cranial radiation therapy.
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</p><p id="CDR0000062864__71">Treatment is divided into the following three phases:</p><ul id="CDR0000062864__72"><li class="half_rhythm"><div>Remission induction.</div></li><li class="half_rhythm"><div>CNS prophylaxis.</div></li><li class="half_rhythm"><div>Postremission (also called remission continuation or maintenance).</div></li></ul><p id="CDR0000062864__73">The average length of treatment for ALL
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varies between 1.5 and 3 years in the effort to eradicate the leukemic cell
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population. Younger adults with ALL may be eligible for selected <a href="http://www.cancer.gov/search/ResultsClinicalTrials.aspx?protocolsearchid=8402089" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">clinical
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trials</a> for childhood ALL. (Refer to the <a href="/books/n/pdqcis/CDR0000062923/#CDR0000062923__1161">Adolescents and Young Adults With ALL</a> section in the PDQ summary on <a href="/books/n/pdqcis/CDR0000062923/">Childhood Acute Lymphoblastic Leukemia Treatment</a> for more information.)
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</p><p id="CDR0000062864__168">Entry into a clinical trial is highly desirable to assure adequate patient treatment and maximal information retrieval from the treatment of this highly responsive, but usually fatal, disease. </p><div id="CDR0000062864__167" class="table"><h3><span class="title">Table 2. Standard Treatment Options for Adult ALL</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK65727.1/table/CDR0000062864__167/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__CDR0000062864__167_lrgtbl__"><table class="no_margin"><thead><tr><th colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062864__58">Disease Status</a></th><th colspan="1" rowspan="1" style="vertical-align:top;">Standard Treatment Options</th></tr></thead><tbody><tr><td colspan="1" rowspan="2" style="vertical-align:top;">Untreated ALL</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062864__87">Remission induction therapy</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062864__101">CNS prophylaxis therapy</a></td></tr><tr><td colspan="1" rowspan="2" style="vertical-align:top;">ALL in remission</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062864__111">Postremission therapy</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062864__130">CNS prophylaxis therapy</a></td></tr><tr><td colspan="1" rowspan="3" style="vertical-align:top;">Recurrent ALL</td><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062864__139">Reinduction chemotherapy</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062864__141">Palliative radiation therapy</a></td></tr><tr><td colspan="1" rowspan="1" style="vertical-align:top;"><a href="#CDR0000062864__143">Dasatinib</a></td></tr></tbody></table></div><div><div><dl class="temp-labeled-list small"><dt></dt><dd><div><p class="no_margin">CNS = central nervous system.</p></div></dd></dl></div></div></div><div id="CDR0000062864_rl_69"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062864_rl_69_1">Clarkson BD, Gee T, Arlin ZA, et al.: Current status of treatment of acute leukemia in adults: an overview of the Memorial experience and review of literature. Crit Rev Oncol Hematol 4 (3): 221-48, 1986. [<a href="https://pubmed.ncbi.nlm.nih.gov/3513984" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3513984</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_69_2">Hoelzer D, Gale RP: Acute lymphoblastic leukemia in adults: recent progress, future directions. Semin Hematol 24 (1): 27-39, 1987. [<a href="https://pubmed.ncbi.nlm.nih.gov/3547671" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3547671</span></a>]</div></li></ol></div></div><div id="CDR0000062864__81"><h2 id="_CDR0000062864__81_">Treatment for Untreated Adult ALL</h2><div id="CDR0000062864__82"><h3>Standard Treatment Options for Untreated Adult ALL</h3><p id="CDR0000062864__83">Standard treatment options for untreated adult acute lymphoblastic leukemia (ALL) include the following:</p><ol id="CDR0000062864__84"><li class="half_rhythm"><div><a href="#CDR0000062864__87">Remission induction therapy</a>, including the following:<ul id="CDR0000062864__206"><li class="half_rhythm"><div>Combination chemotherapy.</div></li><li class="half_rhythm"><div>Imatinib mesylate (for patients with Philadelphia chromosome [Ph1]-positive ALL).</div></li><li class="half_rhythm"><div>Imatinib mesylate combined with combination chemotherapy (for patients with Ph1-positive ALL)</div></li><li class="half_rhythm"><div>Supportive care.</div></li></ul></div></li><li class="half_rhythm"><div><a href="#CDR0000062864__101">Central nervous system (CNS) prophylaxis therapy</a>, including the following:<ul id="CDR0000062864__207"><li class="half_rhythm"><div>Cranial radiation therapy plus intrathecal (IT) methotrexate.</div></li><li class="half_rhythm"><div>High-dose systemic methotrexate and IT methotrexate without cranial radiation therapy.</div></li><li class="half_rhythm"><div>IT chemotherapy alone. </div></li></ul></div></li></ol><div id="CDR0000062864__87"><h4>Remission induction therapy</h4><p id="CDR0000062864__218">Sixty percent to 80% of adults with ALL usually achieve a complete remission (CR) status following appropriate induction therapy. Appropriate initial treatment, usually consisting of a regimen that includes the combination of vincristine, prednisone, and an anthracycline, with or without asparaginase, results in a CR rate of up to 80%. In patients with Ph1-positive ALL, the remission rate is generally greater than 90% when standard induction regimens are combined with <i>Bcr-abl</i> tyrosine kinase inhibitors. In the largest study published to date of Ph1-positive ALL patients, overall survival (OS) for 1,913 adult ALL patients was 39% at 5 years.[<a class="bk_pop" href="#CDR0000062864_rl_81_1">1</a>]</p><p id="CDR0000062864__219">Patients who experience a
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relapse after remission usually die within 1 year, even if a
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second CR is achieved. If there are appropriate available
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donors and if the patient is younger than 55 years, bone marrow
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transplantation may be a consideration in the management of this disease.[<a class="bk_pop" href="#CDR0000062864_rl_81_2">2</a>] Transplant centers performing five or fewer transplants annually usually have
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poorer results than larger centers.[<a class="bk_pop" href="#CDR0000062864_rl_81_3">3</a>] If allogeneic transplant is considered,
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transfusions with blood products from a potential donor should be avoided, if
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possible. [<a class="bk_pop" href="#CDR0000062864_rl_81_4">4</a>-<a class="bk_pop" href="#CDR0000062864_rl_81_10">10</a>]</p><div id="CDR0000062864__169"><h5>Combination chemotherapy</h5><p id="CDR0000062864__88">Most current induction regimens for patients with adult ALL
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include combination chemotherapy with prednisone, vincristine, and an anthracycline. Some regimens, including those used in a Cancer and Leukemia Group B (CALGB) study (CLB-8811), also add
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other drugs, such as asparaginase or cyclophosphamide. Current multiagent
|
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induction regimens result in complete response rates that range from 60% to
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90%.[<a class="bk_pop" href="#CDR0000062864_rl_81_1">1</a>,<a class="bk_pop" href="#CDR0000062864_rl_81_4">4</a>,<a class="bk_pop" href="#CDR0000062864_rl_81_5">5</a>,<a class="bk_pop" href="#CDR0000062864_rl_81_11">11</a>,<a class="bk_pop" href="#CDR0000062864_rl_81_12">12</a>]</p></div><div id="CDR0000062864__170"><h5>Imatinib mesylate </h5><p id="CDR0000062864__171">Imatinib mesylate is often incorporated into the therapeutic plan for patients with Ph1-positive ALL. Imatinib mesylate, an orally available inhibitor of the <i>BCR-ABL</i> tyrosine kinase, has been shown to have clinical activity as a single agent in Ph1-positive ALL.[<a class="bk_pop" href="#CDR0000062864_rl_81_13">13</a>,<a class="bk_pop" href="#CDR0000062864_rl_81_14">14</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000587991/" class="def">Level of evidence: 3iiiDiv</a>] More commonly, particularly in younger patients, imatinib is incorporated into combination chemotherapy regimens. There are several published single-arm studies in which CR rate and survival are compared with historical controls.</p><p id="CDR0000062864__172">Evidence (Imatinib mesylate):</p><p id="CDR0000062864__173">Several studies have suggested that the addition of imatinib to conventional combination chemotherapy induction regimens results in complete response rates, event-free survival rates, and OS rates that are higher than those in historical controls.[<a class="bk_pop" href="#CDR0000062864_rl_81_15">15</a>-
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<a class="bk_pop" href="#CDR0000062864_rl_81_17">17</a>] At the present time, no conclusions can be drawn regarding the optimal imatinib dose or schedule.</p><ol id="CDR0000062864__174"><li class="half_rhythm"><div>In a study of imatinib combined with chemotherapy from the Northern Italy Leukemia Group, patients with newly diagnosed, untreated Ph1-positive ALL were treated with an induction regimen containing idarubicin, vincristine, prednisone, and L-asparaginase.[<a class="bk_pop" href="#CDR0000062864_rl_81_18">18</a>] After accrual of an initial cohort, the study was modified to include the use of imatinib (600 mg per day from days 15 to 21). In consolidation, patients received imatinib (600 mg per day for 7 days) beginning 3 days prior to the start of each course of chemotherapy. <ul id="CDR0000062864__223"><li class="half_rhythm"><div>For all patients who achieved remission, the intent was to proceed to allogeneic transplant when and if an HLA-matched donor could be identified. Patients lacking a donor received an autologous transplant. After completion of chemotherapy and transplant, all patients were to receive maintenance imatinib for as long as tolerated. After 20 patients had accrued to the imatinib arm, L-asparaginase was omitted from the induction regimen from both arms because of toxicity. </div></li><li class="half_rhythm"><div>Outcomes for the first cohort of 35 patients (imatinib-free) were compared to those of the subsequent cohort of 59 (imatinib-treated) patients. For patients treated with imatinib, OS probability was 38% at 5 years (median, 3.1 years) versus 23% in the imatinib-free group (median, 1.1 years; <i>P</i> = .009).[<a class="bk_pop" href="#CDR0000062864_rl_81_18">18</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000561227/" class="def">Level of evidence: 3iii</a>] </div></li><li class="half_rhythm"><div>The drawbacks of this nonrandomized study are the small sample size (94 total patients) and the change in the treatment regimen (omission of L-asparaginase) midway through the study. However, the results suggest that inclusion of imatinib into a relatively standard chemotherapy regimen for newly diagnosed adult patients with Ph1-positive ALL may provide a significant survival advantage.</div></li></ul></div></li><li class="half_rhythm"><div>In another study, ten patients with Ph1-positive ALL and ten patients with chronic myelogenous leukemia in lymphoid blast crisis were treated with doses of imatinib ranging from 300 mg to 1,000 mg per day.[<a class="bk_pop" href="#CDR0000062864_rl_81_13">13</a>] Of these 20 patients, four had complete hematologic remission and ten had marrow responses. Responses were short lived, with the majority of these patients relapsing at a median of 58 days after the start of therapy.</div></li><li class="half_rhythm"><div>In another study, 48 patients with Ph1-positive ALL were treated with 400 mg to 800 mg of imatinib per day.[<a class="bk_pop" href="#CDR0000062864_rl_81_14">14</a>] The overall response rate was 60%, with 9 out of 48 patients (19%) achieving a CR. The responses again were short, with a median duration of 2.2 months.</div></li></ol><p id="CDR0000062864__208">In each of these studies, common toxicities were nausea and liver enzyme abnormalities, which necessitated interruption and/or dose reduction of imatinib.[<a class="bk_pop" href="#CDR0000062864_rl_81_13">13</a>,<a class="bk_pop" href="#CDR0000062864_rl_81_14">14</a>] (Refer to the PDQ summary on <a href="/books/n/pdqcis/CDR0000062747/">Nausea and Vomiting</a> for more information.) Subsequent allogeneic transplant does not appear to be adversely affected by the addition of imatinib to the treatment regimen.</p><p id="CDR0000062864__175">Imatinib is generally incorporated into the treatment of patients with Ph1-positive ALL because of the responses observed in monotherapy trials. If a suitable donor is available,
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allogeneic bone marrow transplantation should be considered because remissions
|
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are generally short with conventional ALL chemotherapy clinical trials.</p></div><div id="CDR0000062864__176"><h5>Supportive care</h5><p id="CDR0000062864__177">Since myelosuppression is an anticipated consequence of both leukemia and
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|
its treatment with chemotherapy, patients must be closely monitored during
|
|
remission induction treatment. Facilities must be available for hematological
|
|
support and for the treatment of infectious complications.
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</p><p id="CDR0000062864__178">Supportive care during remission induction treatment should routinely include
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red blood cell and platelet transfusions, when appropriate.[<a class="bk_pop" href="#CDR0000062864_rl_81_19">19</a>,<a class="bk_pop" href="#CDR0000062864_rl_81_20">20</a>]</p><p id="CDR0000062864__179">Evidence (Supportive care):</p><ol id="CDR0000062864__96"><li class="half_rhythm"><div>Randomized
|
|
clinical trials have shown similar outcomes for patients who received prophylactic
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platelet transfusions at a level of 10,000/mm<sup>3</sup> rather than at a level of
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|
20,000/mm<sup>3</sup>.[<a class="bk_pop" href="#CDR0000062864_rl_81_21">21</a>] </div></li><li class="half_rhythm"><div>The incidence of platelet alloimmunization was
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similar among groups randomly assigned to receive one of the following from random donors:[<a class="bk_pop" href="#CDR0000062864_rl_81_22">22</a>]<ul id="CDR0000062864__200"><li class="half_rhythm"><div>Pooled platelet concentrates.</div></li><li class="half_rhythm"><div>Filtered, pooled platelet concentrates.</div></li><li class="half_rhythm"><div>Ultraviolet B-irradiated, pooled platelet concentrates.</div></li><li class="half_rhythm"><div>Filtered platelets obtained by apheresis.</div></li></ul></div></li></ol><p id="CDR0000062864__98">Empiric broad-spectrum antimicrobial therapy is an absolute necessity for
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|
febrile patients who are profoundly neutropenic.[<a class="bk_pop" href="#CDR0000062864_rl_81_23">23</a>,<a class="bk_pop" href="#CDR0000062864_rl_81_24">24</a>] Careful instruction in
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|
personal hygiene and dental care and in recognizing early signs of infection are
|
|
appropriate for all patients. Elaborate isolation facilities, including
|
|
filtered air, sterile food, and gut flora sterilization, are not routinely
|
|
indicated but may benefit transplant patients.[<a class="bk_pop" href="#CDR0000062864_rl_81_25">25</a>,<a class="bk_pop" href="#CDR0000062864_rl_81_26">26</a>] </p><p id="CDR0000062864__180">Rapid marrow ablation
|
|
with consequent earlier marrow regeneration decreases morbidity and mortality.
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White blood cell transfusions can be beneficial in selected patients with
|
|
aplastic marrow and serious infections that are not responding to
|
|
antibiotics.[<a class="bk_pop" href="#CDR0000062864_rl_81_27">27</a>] Prophylactic oral antibiotics may be appropriate in patients
|
|
with expected prolonged, profound granulocytopenia (<100/mm<sup>3</sup> for 2 weeks), though further studies are necessary.[<a class="bk_pop" href="#CDR0000062864_rl_81_28">28</a>] Serial surveillance cultures may be helpful in detecting the presence or acquisition of resistant organisms in these patients.</p><p id="CDR0000062864__100">As suggested in a CALGB study (CLB-9111), the use of myeloid growth factors during
|
|
remission-induction therapy appears to decrease the time to hematopoietic
|
|
reconstitution.[<a class="bk_pop" href="#CDR0000062864_rl_81_29">29</a>,<a class="bk_pop" href="#CDR0000062864_rl_81_30">30</a>]</p></div></div><div id="CDR0000062864__101"><h4>CNS prophylaxis therapy</h4><p id="CDR0000062864__102">The early institution of CNS prophylaxis is critical to achieve control of
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sanctuary disease.</p></div></div><div id="CDR0000062864__181"><h3>Special Considerations for B-Cell and T-Cell Adult ALL</h3><p id="CDR0000062864__80">Two additional subtypes of adult ALL require special consideration. B-cell ALL, which
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|
expresses surface immunoglobulin and cytogenetic abnormalities such as t(8;14),
|
|
t(2;8), and t(8;22), is not usually cured with typical ALL regimens.
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|
Aggressive brief-duration high-intensity regimens, including those previously used in <a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=77643" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">CLB-9251</a> (<a href="https://clinicaltrials.gov/show/NCT00002494" title="Study NCT00002494" ref="pagearea=body&targetsite=external&targetcat=link&targettype=clinical-trial">NCT00002494</a>), that are similar to those used in aggressive non-Hodgkin lymphoma have shown high response rates and cure rates
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|
(75% CR; 40% failure-free survival).[<a class="bk_pop" href="#CDR0000062864_rl_81_31">31</a>-<a class="bk_pop" href="#CDR0000062864_rl_81_33">33</a>] Similarly, T-cell ALL,
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|
including lymphoblastic lymphoma, has shown high cure rates when
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|
treated with cyclophosphamide-containing regimens.[<a class="bk_pop" href="#CDR0000062864_rl_81_4">4</a>] </p><p id="CDR0000062864__182">Whenever possible, patients with B-cell or T-cell ALL should be entered in clinical trials designed to improve the outcomes
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in these subsets. (Refer to the <a href="/books/n/pdqcis/CDR0000062707/#CDR0000062707__124">Burkitt Lymphoma/Diffuse Small Noncleaved-cell Lymphoma</a> and <a href="/books/n/pdqcis/CDR0000062707/#CDR0000062707__128">Lymphoblastic lymphoma</a> sections in the PDQ summary on <a href="/books/n/pdqcis/CDR0000062707/">Adult Non-Hodgkin Lymphoma
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Treatment</a> for more information.)</p></div><div id="CDR0000062864__TrialSearch_81_sid_5"><h3>Current Clinical Trials</h3><p id="CDR0000062864__TrialSearch_81_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=39077&tt=1&format=2&cn=1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">untreated adult acute lymphoblastic leukemia</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062864__TrialSearch_81_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="CDR0000062864_rl_81"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062864_rl_81_1">Goldstone AH, Richards SM, Lazarus HM, et al.: In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood 111 (4): 1827-33, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18048644" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18048644</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_2">Bortin MM, Horowitz MM, Gale RP, et al.: Changing trends in allogeneic bone marrow transplantation for leukemia in the 1980s. JAMA 268 (5): 607-12, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1321298" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1321298</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_3">Horowitz MM, Przepiorka D, Champlin RE, et al.: Should HLA-identical sibling bone marrow transplants for leukemia be restricted to large centers? Blood 79 (10): 2771-4, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1586723" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1586723</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_4">Larson RA, Dodge RK, Burns CP, et al.: A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood 85 (8): 2025-37, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7718875" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7718875</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_5">Linker CA, Levitt LJ, O'Donnell M, et al.: Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood 78 (11): 2814-22, 1991. 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[<a href="https://pubmed.ncbi.nlm.nih.gov/6347274" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6347274</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_8">Jacobs AD, Gale RP: Recent advances in the biology and treatment of acute lymphoblastic leukemia in adults. N Engl J Med 311 (19): 1219-31, 1984. [<a href="https://pubmed.ncbi.nlm.nih.gov/6092951" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6092951</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_9">Doney K, Buckner CD, Kopecky KJ, et al.: Marrow transplantation for patients with acute lymphoblastic leukemia in first marrow remission. Bone Marrow Transplant 2 (4): 355-63, 1987. [<a href="https://pubmed.ncbi.nlm.nih.gov/3332183" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3332183</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_10">Vernant JP, Marit G, Maraninchi D, et al.: Allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia in first complete remission. J Clin Oncol 6 (2): 227-31, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3276822" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3276822</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_11">Hoelzer D, Thiel E, Löffler H, et al.: Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 71 (1): 123-31, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3422030" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3422030</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_12">Kantarjian H, Thomas D, O'Brien S, et al.: Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer 101 (12): 2788-801, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15481055" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15481055</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_13">Druker BJ, Sawyers CL, Kantarjian H, et al.: Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 344 (14): 1038-42, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11287973" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11287973</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_14">Ottmann OG, Druker BJ, Sawyers CL, et al.: A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood 100 (6): 1965-71, 2002. [<a href="https://pubmed.ncbi.nlm.nih.gov/12200353" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12200353</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_15">Thomas DA, Faderl S, Cortes J, et al.: Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 103 (12): 4396-407, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/14551133" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14551133</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_16">Yanada M, Takeuchi J, Sugiura I, et al.: High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol 24 (3): 460-6, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16344315" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16344315</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_17">Wassmann B, Pfeifer H, Goekbuget N, et al.: Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 108 (5): 1469-77, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16638934" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16638934</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_18">Bassan R, Rossi G, Pogliani EM, et al.: Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00. J Clin Oncol 28 (22): 3644-52, 2010. [<a href="https://pubmed.ncbi.nlm.nih.gov/20606084" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20606084</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_19">Slichter SJ: Controversies in platelet transfusion therapy. Annu Rev Med 31: 509-40, 1980. [<a href="https://pubmed.ncbi.nlm.nih.gov/6994626" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6994626</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_20">Murphy MF, Metcalfe P, Thomas H, et al.: Use of leucocyte-poor blood components and HLA-matched-platelet donors to prevent HLA alloimmunization. Br J Haematol 62 (3): 529-34, 1986. [<a href="https://pubmed.ncbi.nlm.nih.gov/3954967" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3954967</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_21">Rebulla P, Finazzi G, Marangoni F, et al.: The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. N Engl J Med 337 (26): 1870-5, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9407153" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9407153</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_22">Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. The Trial to Reduce Alloimmunization to Platelets Study Group. N Engl J Med 337 (26): 1861-9, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9417523" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9417523</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_23">Hughes WT, Armstrong D, Bodey GP, et al.: From the Infectious Diseases Society of America. Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever. J Infect Dis 161 (3): 381-96, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2179420" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2179420</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_24">Rubin M, Hathorn JW, Pizzo PA: Controversies in the management of febrile neutropenic cancer patients. Cancer Invest 6 (2): 167-84, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3132310" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3132310</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_25">Armstrong D: Symposium on infectious complications of neoplastic disease (Part II). Protected environments are discomforting and expensive and do not offer meaningful protection. Am J Med 76 (4): 685-9, 1984. [<a href="https://pubmed.ncbi.nlm.nih.gov/6424468" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6424468</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_26">Sherertz RJ, Belani A, Kramer BS, et al.: Impact of air filtration on nosocomial Aspergillus infections. Unique risk of bone marrow transplant recipients. Am J Med 83 (4): 709-18, 1987. [<a href="https://pubmed.ncbi.nlm.nih.gov/3314494" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3314494</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_27">Schiffer CA: Granulocyte transfusions: an overlooked therapeutic modality. Transfus Med Rev 4 (1): 2-7, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2134613" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2134613</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_28">Wade JC, Schimpff SC, Hargadon MT, et al.: A comparison of trimethoprim-sulfamethoxazole plus nystatin with gentamicin plus nystatin in the prevention of infections in acute leukemia. N Engl J Med 304 (18): 1057-62, 1981. [<a href="https://pubmed.ncbi.nlm.nih.gov/6782486" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6782486</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_29">Scherrer R, Geissler K, Kyrle PA, et al.: Granulocyte colony-stimulating factor (G-CSF) as an adjunct to induction chemotherapy of adult acute lymphoblastic leukemia (ALL). Ann Hematol 66 (6): 283-9, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/7686404" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7686404</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_30">Larson RA, Dodge RK, Linker CA, et al.: A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111. Blood 92 (5): 1556-64, 1998. [<a href="https://pubmed.ncbi.nlm.nih.gov/9716583" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9716583</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_31">Hoelzer D, Ludwig WD, Thiel E, et al.: Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 87 (2): 495-508, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8555471" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8555471</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_32">Lee EJ, Petroni GR, Schiffer CA, et al.: Brief-duration high-intensity chemotherapy for patients with small noncleaved-cell lymphoma or FAB L3 acute lymphocytic leukemia: results of cancer and leukemia group B study 9251. J Clin Oncol 19 (20): 4014-22, 2001. [<a href="https://pubmed.ncbi.nlm.nih.gov/11600602" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11600602</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_81_33">Thomas DA, Cortes J, O'Brien S, et al.: Hyper-CVAD program in Burkitt's-type adult acute lymphoblastic leukemia. J Clin Oncol 17 (8): 2461-70, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10561310" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10561310</span></a>]</div></li></ol></div></div><div id="CDR0000062864__106"><h2 id="_CDR0000062864__106_">Treatment for Adult ALL in Remission</h2><div id="CDR0000062864__107"><h3>Standard Treatment Options for Adult ALL in Remission</h3><p id="CDR0000062864__108">Standard treatment options for adult acute lymphoblastic leukemia (ALL) in remission include the following:</p><ol id="CDR0000062864__109"><li class="half_rhythm"><div><a href="#CDR0000062864__111">Postremission therapy</a>, including the following: <ul id="CDR0000062864__209"><li class="half_rhythm"><div>Chemotherapy.</div></li><li class="half_rhythm"><div> Ongoing treatment with a <i>Bcr-abl</i> tyrosine kinase inhibitor such as imatinib, nilotinib, or dasatinib.</div></li><li class="half_rhythm"><div>Autologous or allogeneic bone marrow transplant (BMT).</div></li></ul></div></li><li class="half_rhythm"><div><a href="#CDR0000062864__130">Central nervous system (CNS) prophylaxis therapy</a>, including the following:<ul id="CDR0000062864__210"><li class="half_rhythm"><div>Cranial radiation therapy plus intrathecal (IT) methotrexate.</div></li><li class="half_rhythm"><div>High-dose systemic methotrexate and IT methotrexate without cranial
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radiation therapy.</div></li><li class="half_rhythm"><div>IT chemotherapy alone.</div></li></ul></div></li></ol><div id="CDR0000062864__111"><h4>Postremission therapy</h4><p id="CDR0000062864__112">Current approaches to postremission therapy for adult ALL include short-term, relatively intensive chemotherapy followed by any of the following:</p><ul id="CDR0000062864__113"><li class="half_rhythm"><div>Longer-term therapy at lower doses (maintenance therapy).</div></li><li class="half_rhythm"><div>Allogeneic bone marrow transplant.</div></li></ul><p id="CDR0000062864__134">Because the optimal postremission therapy for patients with ALL is still
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unclear, participation in clinical trials should be considered. (Refer to the
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<a href="/books/n/pdqcis/CDR0000062707/#CDR0000062707__273">B-cell (Burkitt) lymphoma</a> section in the PDQ summary on <a href="/books/n/pdqcis/CDR0000062707/">Adult Non-Hodgkin Lymphoma Treatment</a> for more information.)
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</p><p id="CDR0000062864__114">Evidence (Chemotherapy):</p><ol id="CDR0000062864__116"><li class="half_rhythm"><div>Several
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trials, including studies from the Cancer and Leukemia Group B (CLB-8811) and the completed European Cooperative Oncology Group (<a href="http://cancer.gov/clinicaltrials/search/view?version=healthprofessional&cdrid=78099" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">ECOG-2993</a>), of aggressive postremission chemotherapy for adult ALL have confirmed a
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long-term disease-free survival (DFS) rate of approximately 40%.[<a class="bk_pop" href="#CDR0000062864_rl_106_1">1</a>-<a class="bk_pop" href="#CDR0000062864_rl_106_7">7</a>] <ul id="CDR0000062864__201"><li class="half_rhythm"><div>In
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two series,[<a class="bk_pop" href="#CDR0000062864_rl_106_4">4</a>,<a class="bk_pop" href="#CDR0000062864_rl_106_5">5</a>] especially good prognoses were found for patients with T-cell lineage
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ALL, with DFS rates of 50% to 70% for patients receiving
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postremission therapy.</div></li><li class="half_rhythm"><div>These series represent a significant improvement in
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DFS rates over previous, less intensive chemotherapeutic
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approaches.</div></li></ul></div></li><li class="half_rhythm"><div>In contrast, poor cure rates were demonstrated in patients with
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Philadelphia chromosome (Ph1)-positive ALL, B-cell lineage ALL with an L3
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phenotype (surface immunoglobulin positive), and B-cell lineage ALL
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characterized by t(4;11). </div></li></ol><p id="CDR0000062864__202">Administration of the newer dose-intensive schedules can be difficult and should be performed by physicians experienced in these regimens at centers equipped to deal with potential complications. Studies in
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which continuation or maintenance chemotherapy was eliminated had outcomes
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inferior to those with extended treatment durations.[<a class="bk_pop" href="#CDR0000062864_rl_106_8">8</a>,<a class="bk_pop" href="#CDR0000062864_rl_106_9">9</a>] Imatinib has been incorporated into maintenance regimens in patients with Ph1-positive ALL.[<a class="bk_pop" href="#CDR0000062864_rl_106_10">10</a>-
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<a class="bk_pop" href="#CDR0000062864_rl_106_12">12</a>]</p><p id="CDR0000062864__119">Evidence (Allogeneic and autologous BMT):</p><p id="CDR0000062864__203">AlloBMT results in the lowest incidence of leukemic relapse, even when compared
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with a BMT from an identical twin (syngeneic BMT). This
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finding has led to the concept of an immunologic graft-versus-leukemia effect
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similar to graft-versus-host disease (GVHD). The improvement in DFS in patients undergoing alloBMT as primary postremission therapy is
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offset, in part, by the increased morbidity and mortality from GVHD,
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veno-occlusive disease of the liver, and interstitial pneumonitis.[<a class="bk_pop" href="#CDR0000062864_rl_106_13">13</a>]</p><ol id="CDR0000062864__120"><li class="half_rhythm"><div>The results of a series of retrospective and prospective studies published between 1987 and 1994 suggest that alloBMT or autoBMT as postremission therapy offer no survival advantage over intensive chemotherapy, except perhaps for patients with high-risk or Ph1-positive ALL.[<a class="bk_pop" href="#CDR0000062864_rl_106_14">14</a>-<a class="bk_pop" href="#CDR0000062864_rl_106_17">17</a>] This was confirmed in the ECOG-2993 study.[<a class="bk_pop" href="#CDR0000062864_rl_106_7">7</a>]<ul id="CDR0000062864__211"><li class="half_rhythm"><div>The use of alloBMT as primary postremission therapy is limited by both the need for an HLA-matched sibling donor and the increased mortality from alloBMT in patients in their fifth or sixth decade.</div></li><li class="half_rhythm"><div>The mortality from alloBMT using an HLA-matched sibling donor in these studies ranged from 20% to 40%.</div></li></ul></div></li><li class="half_rhythm"><div>Following on the results of earlier studies, the International ALL Trial (ECOG-2993) was launched as an attempt to examine the role of transplant as postremission therapy for ALL more definitively; patients were accrued from 1993 to 2006.[<a class="bk_pop" href="#CDR0000062864_rl_106_7">7</a>] Patients with Ph1-negative ALL between the ages of 15 years and 59 years received identical multiagent induction therapy resembling previously published regimens.[<a class="bk_pop" href="#CDR0000062864_rl_106_1">1</a>-<a class="bk_pop" href="#CDR0000062864_rl_106_3">3</a>] Patients in remission were then eligible for HLA typing; patients with a fully matched sibling donor underwent alloBMT as consolidation therapy. Those patients lacking a donor were randomly assigned to receive either an autoBMT or maintenance chemotherapy. The primary outcome measured was overall survival (OS); event-free survival, relapse rate, and nonrelapse mortality were secondary outcomes. A total of 1,929 patients were registered and stratified according to age, white blood cell (WBC) count, and time to remission. High-risk patients were defined as those having a high WBC count at presentation or those older than 35 years.<ol id="CDR0000062864__122" class="lower-alpha"><li class="half_rhythm"><div>Ninety percent of patients in this study achieved remission after induction therapy. Of these patients, 443 had an HLA-identical sibling, 310 of whom underwent an alloBMT. For the 456 patients in remission who were eligible for transplant but lacked a donor, 227 received chemotherapy alone, while 229 underwent an autoBMT.</div></li><li class="half_rhythm"><div> By donor-to-no-donor analysis, standard-risk ALL patients with an HLA-identical sibling had a 5-year OS of 53% compared with 45% for patients lacking a donor (<i>P</i> = .01). </div></li><li class="half_rhythm"><div>In a subgroup analysis, the advantage for patients with standard-risk ALL who had donors remained significant (OS = 62% vs. 52%; <i>P</i> = .02). <ul id="CDR0000062864__212"><li class="half_rhythm"><div>For patients with high-risk disease (older than 35 years or high WBC count), the difference in OS was 41% versus 35% (donor vs. no donor), but was not significant (<i>P</i> = .2).</div></li><li class="half_rhythm"><div>Relapse rates were significantly lower (<i>P</i> < .00005) for both standard- and high-risk patients with HLA-matched donors.</div></li></ul></div></li><li class="half_rhythm"><div>In contrast to alloBMT, autoBMT was less effective than maintenance chemotherapy as postremission treatment (5-year OS = 46% for chemotherapy vs. 37% for autoBMT; <i>P</i> = .03).</div></li><li class="half_rhythm"><div>The results of this trial suggest the existence of a graft-versus-leukemia effect for adult Ph1-negative ALL and support the use of sibling donor alloBMT as the consolidation therapy providing the greatest chance for long-term survival for patients with standard-risk adult ALL in first remission.[<a class="bk_pop" href="#CDR0000062864_rl_106_7">7</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335132/" class="def">Level of evidence: 2A</a>]</div></li><li class="half_rhythm"><div>The results also suggest that in the absence of a sibling donor, maintenance chemotherapy is preferable to autoBMT as postremission therapy.[<a class="bk_pop" href="#CDR0000062864_rl_106_7">7</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335132/" class="def">Level of evidence: 2A</a>]</div></li></ol></div></li></ol><p id="CDR0000062864__125">The use of matched unrelated donors for alloBMT is
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currently under evaluation but, because of its current high treatment-related
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morbidity and mortality, it is reserved for patients in second remission or
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beyond. The dose of total-body radiation therapy administered is associated with the
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incidence of acute and chronic GVHD and may be an independent predictor of
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leukemia-free survival.[<a class="bk_pop" href="#CDR0000062864_rl_106_18">18</a>][<a href="/books/n/pdqcis/glossary_loe/def-item/glossary_loe_CDR0000335145/" class="def">Level of evidence: 3iiB</a>]
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</p><p id="CDR0000062864__127">Evidence (B-cell ALL):</p><p id="CDR0000062864__204">Aggressive cyclophosphamide-based regimens similar to those used in aggressive
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non-Hodgkin lymphoma have shown improved outcome of prolonged DFS for patients with B-cell ALL (L3 morphology, surface immunoglobulin
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positive).[<a class="bk_pop" href="#CDR0000062864_rl_106_19">19</a>]</p><ol id="CDR0000062864__128"><li class="half_rhythm"><div>Retrospectively reviewing three sequential cooperative group trials
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from Germany, one group of investigators found the following:[<a class="bk_pop" href="#CDR0000062864_rl_106_19">19</a>]<ul id="CDR0000062864__213"><li class="half_rhythm"><div>A marked improvement in survival,
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from zero survivors in a 1981 study that used standard pediatric therapy and
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lasted 2.5 years, to a 50% survival rate in two subsequent trials that used
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rapidly alternating lymphoma-like chemotherapy and were completed within 6
|
|
months. </div></li></ul></div></li></ol></div><div id="CDR0000062864__130"><h4>CNS prophylaxis therapy</h4><p id="CDR0000062864__131">The early institution of CNS prophylaxis is critical to achieve control of
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sanctuary disease. Some authors have suggested that there is a subgroup of
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patients at low risk for CNS relapse for whom CNS prophylaxis may not be
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necessary. However, this concept has not been tested prospectively.[<a class="bk_pop" href="#CDR0000062864_rl_106_20">20</a>]</p><p id="CDR0000062864__132">Aggressive CNS prophylaxis remains a prominent component of treatment.[<a class="bk_pop" href="#CDR0000062864_rl_106_19">19</a>]
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This report, which requires confirmation in other cooperative group settings,
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is encouraging for patients with L3 ALL. Patients with surface immunoglobulin
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and L1 or L2 morphology did not benefit from this regimen. Similarly, patients
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with L3 morphology and immunophenotype, but unusual cytogenetic features, were
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not cured with this approach. A WBC count of less than 50,000 per
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microliter predicted improved leukemia-free survival in a univariate analysis.</p></div></div><div id="CDR0000062864__TrialSearch_106_sid_6"><h3>Current Clinical Trials</h3><p id="CDR0000062864__TrialSearch_106_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=39084&tt=1&format=2&cn=1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">adult acute lymphoblastic leukemia in remission</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062864__TrialSearch_106_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="CDR0000062864_rl_106"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062864_rl_106_1">Gaynor J, Chapman D, Little C, et al.: A cause-specific hazard rate analysis of prognostic factors among 199 adults with acute lymphoblastic leukemia: the Memorial Hospital experience since 1969. J Clin Oncol 6 (6): 1014-30, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3163722" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3163722</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_2">Hoelzer D, Thiel E, Löffler H, et al.: Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 71 (1): 123-31, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3422030" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3422030</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_3">Linker CA, Levitt LJ, O'Donnell M, et al.: Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report. Blood 78 (11): 2814-22, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/1835410" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1835410</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_4">Zhang MJ, Hoelzer D, Horowitz MM, et al.: Long-term follow-up of adults with acute lymphoblastic leukemia in first remission treated with chemotherapy or bone marrow transplantation. The Acute Lymphoblastic Leukemia Working Committee. Ann Intern Med 123 (6): 428-31, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7639442" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7639442</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_5">Larson RA, Dodge RK, Burns CP, et al.: A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood 85 (8): 2025-37, 1995. [<a href="https://pubmed.ncbi.nlm.nih.gov/7718875" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7718875</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_6">Kantarjian H, Thomas D, O'Brien S, et al.: Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer 101 (12): 2788-801, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/15481055" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15481055</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_7">Goldstone AH, Richards SM, Lazarus HM, et al.: In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood 111 (4): 1827-33, 2008. [<a href="https://pubmed.ncbi.nlm.nih.gov/18048644" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18048644</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_8">Cuttner J, Mick R, Budman DR, et al.: Phase III trial of brief intensive treatment of adult acute lymphocytic leukemia comparing daunorubicin and mitoxantrone: a CALGB Study. Leukemia 5 (5): 425-31, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/2033963" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2033963</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_9">Dekker AW, van't Veer MB, Sizoo W, et al.: Intensive postremission chemotherapy without maintenance therapy in adults with acute lymphoblastic leukemia. Dutch Hemato-Oncology Research Group. J Clin Oncol 15 (2): 476-82, 1997. [<a href="https://pubmed.ncbi.nlm.nih.gov/9053468" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9053468</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_10">Thomas DA, Faderl S, Cortes J, et al.: Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 103 (12): 4396-407, 2004. [<a href="https://pubmed.ncbi.nlm.nih.gov/14551133" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14551133</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_11">Yanada M, Takeuchi J, Sugiura I, et al.: High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol 24 (3): 460-6, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16344315" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16344315</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_12">Wassmann B, Pfeifer H, Goekbuget N, et al.: Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 108 (5): 1469-77, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16638934" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16638934</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_13">Finiewicz KJ, Larson RA: Dose-intensive therapy for adult acute lymphoblastic leukemia. Semin Oncol 26 (1): 6-20, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10073558" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10073558</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_14">Horowitz MM, Messerer D, Hoelzer D, et al.: Chemotherapy compared with bone marrow transplantation for adults with acute lymphoblastic leukemia in first remission. Ann Intern Med 115 (1): 13-8, 1991. [<a href="https://pubmed.ncbi.nlm.nih.gov/2048858" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2048858</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_15">Sebban C, Lepage E, Vernant JP, et al.: Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. French Group of Therapy of Adult Acute Lymphoblastic Leukemia. J Clin Oncol 12 (12): 2580-7, 1994. [<a href="https://pubmed.ncbi.nlm.nih.gov/7989932" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7989932</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_16">Forman SJ, O'Donnell MR, Nademanee AP, et al.: Bone marrow transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 70 (2): 587-8, 1987. [<a href="https://pubmed.ncbi.nlm.nih.gov/3300815" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3300815</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_17">Fière D, Lepage E, Sebban C, et al.: Adult acute lymphoblastic leukemia: a multicentric randomized trial testing bone marrow transplantation as postremission therapy. The French Group on Therapy for Adult Acute Lymphoblastic Leukemia. J Clin Oncol 11 (10): 1990-2001, 1993. [<a href="https://pubmed.ncbi.nlm.nih.gov/8410124" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8410124</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_18">Corvò R, Paoli G, Barra S, et al.: Total body irradiation correlates with chronic graft versus host disease and affects prognosis of patients with acute lymphoblastic leukemia receiving an HLA identical allogeneic bone marrow transplant. Int J Radiat Oncol Biol Phys 43 (3): 497-503, 1999. [<a href="https://pubmed.ncbi.nlm.nih.gov/10078628" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10078628</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_19">Hoelzer D, Ludwig WD, Thiel E, et al.: Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 87 (2): 495-508, 1996. [<a href="https://pubmed.ncbi.nlm.nih.gov/8555471" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8555471</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_106_20">Kantarjian HM, Walters RS, Smith TL, et al.: Identification of risk groups for development of central nervous system leukemia in adults with acute lymphocytic leukemia. Blood 72 (5): 1784-9, 1988. [<a href="https://pubmed.ncbi.nlm.nih.gov/3052630" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3052630</span></a>]</div></li></ol></div></div><div id="CDR0000062864__135"><h2 id="_CDR0000062864__135_">Treatment for Recurrent Adult ALL</h2><div id="CDR0000062864__136"><h3>Standard Treatment Options for Recurrent Adult ALL</h3><p id="CDR0000062864__137">Standard treatment options for recurrent adult acute lymphoblastic leukemia (ALL) include the following:</p><ol id="CDR0000062864__138"><li class="half_rhythm"><div><a href="#CDR0000062864__139">Reinduction chemotherapy </a> followed by allogeneic bone marrow transplantation (alloBMT).</div></li><li class="half_rhythm"><div><a href="#CDR0000062864__141">Palliative radiation therapy</a> (for patients with symptomatic recurrence).</div></li><li class="half_rhythm"><div><a href="#CDR0000062864__143">Dasatinib</a> (for patients with Philadelphia chromosome [Ph1]-positive ALL).</div></li></ol><div id="CDR0000062864__139"><h4>Reinduction chemotherapy</h4><p id="CDR0000062864__140">Patients with ALL who experience a relapse following chemotherapy and maintenance
|
|
therapy are unlikely to be cured by further chemotherapy alone. These patients
|
|
should be considered for reinduction chemotherapy followed by alloBMT.</p></div><div id="CDR0000062864__141"><h4>Palliative radiation therapy</h4><p id="CDR0000062864__142">Low-dose palliative radiation
|
|
therapy may be considered in patients with symptomatic recurrence either within
|
|
or outside the central nervous system.[<a class="bk_pop" href="#CDR0000062864_rl_135_1">1</a>]</p></div><div id="CDR0000062864__143"><h4>Dasatinib</h4><p id="CDR0000062864__144">Patients with Ph1-positive ALL will often be taking imatinib at the time of relapse and thus will have imatinib-resistant disease. Dasatinib, a novel tyrosine kinase inhibitor with efficacy against several different imatinib-resistant <i>BCR-ABL</i> mutations, has been approved for use in Ph1-positive ALL patients who are resistant to or intolerant of imatinib. The approval was based on a series of trials involving patients with chronic myelogenous leukemia, one of which included small numbers of patients with lymphoid blast crisis or Ph1-positive ALL.</p><p id="CDR0000062864__145">Evidence (Dasatinib):</p><ol id="CDR0000062864__146"><li class="half_rhythm"><div>In one study, ten patients were treated with dose-escalated dasatinib.[<a class="bk_pop" href="#CDR0000062864_rl_135_2">2</a>] Seven of these patients had a complete hematologic response (<5% marrow blasts with normal peripheral blood cell counts), three of whom had a complete cytogenetic response.<ul id="CDR0000062864__205"><li class="half_rhythm"><div>The common toxicities were reversible myelosuppression (89%) and pleural effusions (21%).</div></li><li class="half_rhythm"><div>Virtually all of these patients relapsed within 6 months of the start of treatment with dasatinib.</div></li></ul></div></li></ol></div></div><div id="CDR0000062864__148"><h3>Treatment Options Under Clinical Evaluation for Recurrent Adult ALL</h3><p id="CDR0000062864__149">Patients for whom an HLA-matched donor is not
|
|
available are excellent candidates for enrollment in clinical trials that are
|
|
studying the following:[<a class="bk_pop" href="#CDR0000062864_rl_135_3">3</a>-<a class="bk_pop" href="#CDR0000062864_rl_135_9">9</a>]</p><ol id="CDR0000062864__150"><li class="half_rhythm"><div>Autologous transplantation.</div></li><li class="half_rhythm"><div>Immunomodulation.</div></li><li class="half_rhythm"><div>Novel
|
|
chemotherapeutic or biological agents.</div></li></ol></div><div id="CDR0000062864__TrialSearch_135_sid_7"><h3>Current Clinical Trials</h3><p id="CDR0000062864__TrialSearch_135_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=38716&tt=1&format=2&cn=1" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">recurrent adult acute lymphoblastic leukemia</a>. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.</p><p id="CDR0000062864__TrialSearch_135_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="CDR0000062864_rl_135"><h3>References</h3><ol><li><div class="bk_ref" id="CDR0000062864_rl_135_1">Gray JR, Wallner KE: Reversal of cranial nerve dysfunction with radiation therapy in adults with lymphoma and leukemia. Int J Radiat Oncol Biol Phys 19 (2): 439-44, 1990. [<a href="https://pubmed.ncbi.nlm.nih.gov/2394621" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2394621</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_135_2">Talpaz M, Shah NP, Kantarjian H, et al.: Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 354 (24): 2531-41, 2006. [<a href="https://pubmed.ncbi.nlm.nih.gov/16775234" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16775234</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_135_3">Herzig RH, Bortin MM, Barrett AJ, et al.: Bone-marrow transplantation in high-risk acute lymphoblastic leukaemia in first and second remission. Lancet 1 (8536): 786-9, 1987. [<a href="https://pubmed.ncbi.nlm.nih.gov/2882192" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2882192</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_135_4">Thomas ED, Sanders JE, Flournoy N, et al.: Marrow transplantation for patients with acute lymphoblastic leukemia: a long-term follow-up. Blood 62 (5): 1139-41, 1983. [<a href="https://pubmed.ncbi.nlm.nih.gov/6354306" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6354306</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_135_5">Barrett AJ, Horowitz MM, Gale RP, et al.: Marrow transplantation for acute lymphoblastic leukemia: factors affecting relapse and survival. Blood 74 (2): 862-71, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2665858" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2665858</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_135_6">Dinsmore R, Kirkpatrick D, Flomenberg N, et al.: Allogeneic bone marrow transplantation for patients with acute lymphoblastic leukemia. Blood 62 (2): 381-8, 1983. [<a href="https://pubmed.ncbi.nlm.nih.gov/6347274" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 6347274</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_135_7">Sallan SE, Niemeyer CM, Billett AL, et al.: Autologous bone marrow transplantation for acute lymphoblastic leukemia. J Clin Oncol 7 (11): 1594-601, 1989. [<a href="https://pubmed.ncbi.nlm.nih.gov/2809677" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 2809677</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_135_8">Paciucci PA, Keaveney C, Cuttner J, et al.: Mitoxantrone, vincristine, and prednisone in adults with relapsed or primarily refractory acute lymphocytic leukemia and terminal deoxynucleotidyl transferase positive blastic phase chronic myelocytic leukemia. Cancer Res 47 (19): 5234-7, 1987. [<a href="https://pubmed.ncbi.nlm.nih.gov/3476201" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 3476201</span></a>]</div></li><li><div class="bk_ref" id="CDR0000062864_rl_135_9">Biggs JC, Horowitz MM, Gale RP, et al.: Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy. Blood 80 (4): 1090-3, 1992. [<a href="https://pubmed.ncbi.nlm.nih.gov/1498326" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1498326</span></a>]</div></li></ol></div></div><div id="CDR0000062864__151"><h2 id="_CDR0000062864__151_">Changes to This Summary (04/17/2015)</h2><p id="CDR0000062864__197">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="CDR0000062864__246"><b><a href="#CDR0000062864__1">General Information About Adult Acute Lymphoblastic Leukemia (ALL)</a></b></p><p id="CDR0000062864__247">Added <a href="#CDR0000062864__243">Related Summaries</a> as a new subsection.</p><p id="CDR0000062864__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="#CDR0000062864__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="CDR0000062864__AboutThis_1"><h2 id="_CDR0000062864__AboutThis_1_">About This PDQ Summary</h2><div id="CDR0000062864__AboutThis_2"><h3>Purpose of This Summary</h3><p id="CDR0000062864__AboutThis_3">This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of acute lymphoblastic leukemia. 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="CDR0000062864__AboutThis_4"><h3>Reviewers and Updates</h3><p id="CDR0000062864__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="CDR0000062864__AboutThis_22"> Board members review recently published articles each month to determine whether an article should:</p><ul id="CDR0000062864__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="CDR0000062864__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 Acute Lymphoblastic Leukemia Treatment is:</p><ul><li class="half_rhythm"><div>Mikkael A. Sekeres, MD, MS (Cleveland Clinic Taussig Cancer Institute)</div></li></ul><p id="CDR0000062864__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="CDR0000062864__AboutThis_10"><h3>Levels of Evidence</h3><p id="CDR0000062864__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="CDR0000062864__AboutThis_12"><h3>Permission to Use This Summary</h3><p id="CDR0000062864__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="CDR0000062864__AboutThis_14">The preferred citation for this PDQ summary is:</p><p id="CDR0000062864__AboutThis_15">National Cancer Institute: PDQ® Adult Acute Lymphoblastic Leukemia Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: <a href="http://www.cancer.gov/types/leukemia/hp/adult-all-treatment-pdq" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">http://www.cancer.gov/types/leukemia/hp/adult-all-treatment-pdq</a>. Accessed <MM/DD/YYYY>.</p><p id="CDR0000062864__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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<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/NBK65727.1/?report=reader">PubReader</a></li><li><a href="/books/NBK65727.1/?report=printable">Print View</a></li><li><a data-jig="ncbidialog" href="#_ncbi_dlg_citbx_NBK65727" data-jigconfig="width:400,modal:true">Cite this Page</a><div id="_ncbi_dlg_citbx_NBK65727" style="display:none" title="Cite this Page"><div class="bk_tt">PDQ Adult Treatment Editorial Board. 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ALL</a></li><li><a href="#CDR0000062864__151" ref="log$=inpage&link_id=inpage">Changes to This Summary (04/17/2015)</a></li><li><a href="#CDR0000062864__AboutThis_1" ref="log$=inpage&link_id=inpage">About This PDQ Summary</a></li><li><a href="#CDR0000062864__GetMore_3" ref="log$=inpage&link_id=inpage">Get More Information From NCI</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related publications</span></h3></div><a name="Shutter" sid="1" href="#" class="portlet_shutter" title="Show/hide content" remembercollapsed="true" pgsec_name="document-links" id="Shutter"></a></div><div class="portlet_content"><ul xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="simple-list"><li><a href="/books/NBK65844/">Patient Version</a></li></ul></div></div><div class="portlet"><div class="portlet_head"><div class="portlet_title"><h3><span>Related information</span></h3></div><a 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xmlns:np="http://ncbi.gov/portal/XSLT/namespace" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="cit">PDQ Cancer Information Summaries. 2002</em></div></div></li><li class="brieflinkpopper two_line"><a class="brieflinkpopperctrl" href="/pubmed/26389432" ref="ordinalpos=1&linkpos=2&log$=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> Acute Myeloid Leukemia 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> Acute Myeloid Leukemia 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/26389470" 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> Chronic Lymphocytic Leukemia 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> Chronic Lymphocytic Leukemia Treatment (PDQ®): Health Professional Version.<div class="brieflinkpopdesc"><em 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