{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T15:48:50Z","timestamp":1770479330553,"version":"3.49.0"},"reference-count":40,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) includes at least one-quarter of all adults with ALL. Until recently, conventional chemotherapy programs that have been effective in other precursor B-cell ALL cases have been unable to cure patients with this diagnosis. Allogeneic stem cell transplantation early in first remission has been the recommended therapy. The availability of imatinib mesylate and other tyrosine kinase inhibitors and small molecules that affect the BCR\/ABL signaling pathways may be changing the treatment paradigm and the prognosis for these patients. The results from clinical trials using imatinib in the frontline setting and in relapsed patients as well as preliminary experience treating imatinib-resistant Ph+ ALL will be described.<\/jats:p>","DOI":"10.1182\/asheducation-2005.1.118","type":"journal-article","created":{"date-parts":[[2005,11,23]],"date-time":"2005-11-23T01:29:34Z","timestamp":1132709374000},"page":"118-122","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":44,"title":["Treatment of Philadelphia Chromosome\u2013Positive Acute Lymphoblastic Leukemia"],"prefix":"10.1182","volume":"2005","author":[{"given":"Oliver G.","family":"Ottmann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Wassmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2019111704475189600_R1","unstructured":"Nowell PC, Hungerford D. A minute chromosome in human chronic granulocytic leukemias. Science. 1960;14:97."},{"key":"2019111704475189600_R2","doi-asserted-by":"crossref","unstructured":"Radich JP. Philadelphia chromosome-positive acute lymphocytic leukemia. Hematol Oncol Clin North Am. 2001;15:21\u201336.","DOI":"10.1016\/S0889-8588(05)70198-2"},{"key":"2019111704475189600_R3","unstructured":"Hoelzer D, Go\u0308kbuget N. Treatment of elderly patients with acute lymphoblastic leukemia. ASCO Education Book, 41st Annual Meeting May 13\u201317, 2005:533\u2013539."},{"key":"2019111704475189600_R4","doi-asserted-by":"crossref","unstructured":"Hoelzer D, Go\u0308kbuget N. Recent approaches in acute lymphoblastic leukemia in adults. Crit Rev Oncol Hematol. 2000;36:49\u201358.","DOI":"10.1016\/S1040-8428(00)00097-4"},{"key":"2019111704475189600_R5","doi-asserted-by":"crossref","unstructured":"Glei\u00dfner B, Go\u0308kbuget N, Bartram CR, et al. Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood. 2002;99:1536\u20131543.","DOI":"10.1182\/blood.V99.5.1536"},{"key":"2019111704475189600_R6","doi-asserted-by":"crossref","unstructured":"Dombret H, Gabert J, Boiron JM, et al. Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia\u2014results of the prospective multicenter LALA-94 trial. Blood. 2002;100:2357\u20132366.","DOI":"10.1182\/blood-2002-03-0704"},{"key":"2019111704475189600_R7","doi-asserted-by":"crossref","unstructured":"Kantarjian HM, O\u2019Brien S, Smith TL, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol. 2000;18:547\u2013561.","DOI":"10.1200\/JCO.2000.18.3.547"},{"key":"2019111704475189600_R8","doi-asserted-by":"crossref","unstructured":"Avivi I, Goldstone AH. Bone marrow transplant in Ph+ ALL patients. Bone Marrow Transplant. 2003;31:623\u2013632.","DOI":"10.1038\/sj.bmt.1703899"},{"key":"2019111704475189600_R9","unstructured":"Martin TG, Gajewski JL. Allogeneic stem cell transplantation for acute lymphocytic leukemia in adults. Advances in the treatment of adult acute lymphocytic leukemia, Hematol\/ Oncol Clin North Am. 2001;15:97\u2013120."},{"key":"2019111704475189600_R10","doi-asserted-by":"crossref","unstructured":"Cornelissen JJ, Carston M, Kollman C, et al. Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome. Blood. 2001;97:1572\u20131577.","DOI":"10.1182\/blood.V97.6.1572"},{"key":"2019111704475189600_R11","unstructured":"Martin H, Atta J, Klein SA, et al. Autologous BMT\/PBSCT in 40 patients with bcr-abl positive acute lymphoblastic leukemia: long-term follow-up of a GMALL study [abstract]. Hematology. 2001;I:187."},{"key":"2019111704475189600_R12","doi-asserted-by":"crossref","unstructured":"Druker BJ, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996;2:561\u2013566.","DOI":"10.1038\/nm0596-561"},{"key":"2019111704475189600_R13","doi-asserted-by":"crossref","unstructured":"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. 2001;344:1038\u20131042.","DOI":"10.1056\/NEJM200104053441402"},{"key":"2019111704475189600_R14","doi-asserted-by":"crossref","unstructured":"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. 2002;100:1965\u20131971.","DOI":"10.1182\/blood-2001-12-0181"},{"key":"2019111704475189600_R15","doi-asserted-by":"crossref","unstructured":"Wassmann B, Pfeifer H, Scheuring UJ, et al. Early prediction of response in patients with relapsed or refractory Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ALL) treated with imatinib mesylate (Glivec). Blood. 2004;103:1495\u20131498.","DOI":"10.1182\/blood-2003-01-0154"},{"key":"2019111704475189600_R16","doi-asserted-by":"crossref","unstructured":"Thomas D, Faderl S, Cortes J, et al. Update of the hyper-CVAD and imatinib mesylate regimen in Philadelphia (Ph) positive acute lymphocytic leukemia (ALL) [abstract]. Blood. 2004;104. Abstr. 2738.","DOI":"10.1182\/blood.V104.11.2738.2738"},{"key":"2019111704475189600_R17","doi-asserted-by":"crossref","unstructured":"Towatari M, Yanada M, Usui N, et al. Combination of intensive chemotherapy and imatinib can rapidly induce high-quality complete remission for a majority of patients with newly diagnosed BCR-ABL-positive acute lymphoblastic. Blood. 2004;104:3507\u20133535.","DOI":"10.1182\/blood-2004-04-1389"},{"key":"2019111704475189600_R18","doi-asserted-by":"crossref","unstructured":"Ribera J-M, Oriol A, Gonzalez M, et al. Treatment of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) with concurrent chemotherapy and imatinib mesylate [abstract]. Blood. 2004;104. Abstr. 4483.","DOI":"10.1182\/blood.V104.11.4483.4483"},{"key":"2019111704475189600_R19","doi-asserted-by":"crossref","unstructured":"Ottmann OG, Wassmann B, Pfeifer H, et al. Imatinib given concurrently with induction chemotherapy is superior to imatinib subsequent to induction and consolidation in newly diagnosed Philadelphia-Positive acute lymphoblastic leukemia (PH+ALL) [abstract]. Blood. 2004;104. Abstr. 685.","DOI":"10.1182\/blood.V104.11.685.685"},{"key":"2019111704475189600_R20","doi-asserted-by":"crossref","unstructured":"Vignetti M, Fazi P, Meloni G, Chiarenza A, Malagola M et al. Dramatic improvement in CR rate and CR duration with imatinib in adult and elderly Ph+ ALL patients: results of the GIMEMA prospective study LAL0201 [abstract]. Blood2004;104. Abstr. 2739.","DOI":"10.1182\/blood.V104.11.2739.2739"},{"key":"2019111704475189600_R21","unstructured":"Ottmann OG, Wassmann B, Go\u0308kbuget N, et al. A randomized phase II study comparing Imatinib with chemotherapy as induction therapy in elderly patients with newly diagnosed Philadelphia-positive acute lymphoid leukemias (Ph+ALL) [abstract]. Hematology J. 2004;5:S112."},{"key":"2019111704475189600_R22","doi-asserted-by":"crossref","unstructured":"Dombret H, Witz F, De Botton S, et al. Imatinib combined with intensive HAM chemotherapy as consolidation of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL). preliminary results of the AFR03 phase I\/II study. Blood. 2004;104. Abstr. 2741.","DOI":"10.1182\/blood.V104.11.2741.2741"},{"key":"2019111704475189600_R23","doi-asserted-by":"crossref","unstructured":"Delannoy A, Lhe\u0301ritier V, Thomas X, et al. Treatment of Philadelphia-positive acute lymphocytic leukemia (Ph+ ALL) in the elderly with imatinib mesylate (STI571) and chemotherapy. an interim analysis of the GRAALL AFR09 Trial [abstract]. Blood. 2004;104. Abstr. 2742.","DOI":"10.1182\/blood.V104.11.2742.2742"},{"key":"2019111704475189600_R24","doi-asserted-by":"crossref","unstructured":"Lee S, Kim YJ, Min CK, et al. The effect of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation in adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2005;105:3449\u20133457.","DOI":"10.1182\/blood-2004-09-3785"},{"key":"2019111704475189600_R25","doi-asserted-by":"crossref","unstructured":"Hofmann WK, Komor M, Hoelzer D, Ottmann OG. Mechanisms of resistance to STI571 (Imatinib) in Philadelphia-chromosome positive acute lymphoblastic leukemia. Leuk Lymphoma. 2004;45:655\u2013660.","DOI":"10.1080\/10428190310001625755"},{"key":"2019111704475189600_R26","doi-asserted-by":"crossref","unstructured":"von Bubnoff N, Peschel C, Duyster J. Resistance of Philadelphia-chromosome positive leukemia towards the kinase inhibitor imatinib (STI571, Glivec): a targeted oncoprotein strikes back. Leukemia. 2003;17:829\u2013838.","DOI":"10.1038\/sj.leu.2402889"},{"key":"2019111704475189600_R27","doi-asserted-by":"crossref","unstructured":"Hofmann WK, Komor M, Wassmann B, et al. Presence of the BCR-ABL mutation Glu255Lys prior to STI571 (imatinib) treatment in patients with Ph+ acute lymphoblastic leukemia. Blood. 2003;102:659\u2013661.","DOI":"10.1182\/blood-2002-06-1756"},{"key":"2019111704475189600_R28","unstructured":"Pfeifer H, Wassmann B, Hofmann WK, et al. Risk and prognosis of central nervous system (CNS) leukemia in patients with Philadelphia chromosome positive (Ph+) acute leukemias treated with imatinib mesylate (GlivecTM). Clin Cancer Res. 2003;9:4674\u20134681."},{"key":"2019111704475189600_R29","doi-asserted-by":"crossref","unstructured":"Radich J, Gehly G, Lee A, et al. Detection of bcr-abl transcripts in Philadelphia chromosome positive acute lymphoblastic leukemia after marrow transplantation. Blood. 1997;89:2602\u20132609.","DOI":"10.1182\/blood.V89.7.2602"},{"key":"2019111704475189600_R30","unstructured":"Wassmann B, Pfeifer H, Stadler M, et al. Early molecular response to post-transplant imatinib determines outcome in MRD-positive Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL). Blood First Edition Paper, prepublished online April 7, 2005; Blood-2004-05-1746."},{"key":"2019111704475189600_R31","doi-asserted-by":"crossref","unstructured":"Visani G, Isidori A, Malagola M, et al. Efficacy of imatinb mesylate (STI571) in conjunction with alpha-interferon: long-term quantitative molecular remission in relapsed p190 BCR-ABL positive acute lymphoblastic leukemia. Leukemia. 2002;16:2159\u20132160.","DOI":"10.1038\/sj.leu.2402729"},{"key":"2019111704475189600_R32","doi-asserted-by":"crossref","unstructured":"Wassmann B, Scheuring U, Pfeifer H, et al. Efficacy and safety of Imatinib mesylate (Gliveca\u0308) in combination with Interferon-\u03b1 (IFN-\u03b1) in Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ALL). Leukemia. 2003;17:1919\u20131924.","DOI":"10.1038\/sj.leu.2403093"},{"key":"2019111704475189600_R33","doi-asserted-by":"crossref","unstructured":"Garcia-Manero G, Thomas DA. Salvage therapy for refractory or relapsed acute lymphocytic leukemia. Hematol\/Oncol Clin North Am. 2001;15:163\u2013205.","DOI":"10.1016\/S0889-8588(05)70204-5"},{"key":"2019111704475189600_R34","doi-asserted-by":"crossref","unstructured":"Wassmann B, Pfeifer H, Scheuring U, et al. Therapy with imatinib mesylate (Glivec) preceding allogeneic stem cell transplantation (SCT) in relapsed or refractory Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL). Leukemia. 2002;16:2358\u20132365.","DOI":"10.1038\/sj.leu.2402770"},{"key":"2019111704475189600_R35","doi-asserted-by":"crossref","unstructured":"Weisberg E, Manley PW, Breitenstein W, et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell. 2005;7:129\u2013141.","DOI":"10.1016\/j.ccr.2005.01.007"},{"key":"2019111704475189600_R36","doi-asserted-by":"crossref","unstructured":"Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. 2004;305:399\u2013401.","DOI":"10.1126\/science.1099480"},{"key":"2019111704475189600_R37","doi-asserted-by":"crossref","unstructured":"Giles F, Kantarjian H, Wassmann B, et al. A phase I\/II study of AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl, on a continuous daily dosing schedule in adult patients (pts) with imatinib-resistant advanced phase chronic myeloid leukemia (CML) or relapsed\/refractory Philadelphia chromosome (Ph+) acute lymphocytic leukemia (ALL) [abstract]. Blood2004;104. Abstr. 22.","DOI":"10.1182\/blood.V104.11.22.22"},{"key":"2019111704475189600_R38","doi-asserted-by":"crossref","unstructured":"Talpaz M, Kantarjian H, Shah NP, et al. Hematologic and cytogenetic responses in imatinib-resistant accelerated and blast phase chronic myeloid leukemia (CML) patients treated with the dual SRC\/ABL kinase inhibitor BMS-354825: results from a phase I dose escalation study [abstract]. Blood2004;104. Abstr. 20.","DOI":"10.1182\/blood.V104.11.20.20"},{"key":"2019111704475189600_R39","doi-asserted-by":"crossref","unstructured":"Hoover RR, Mahon FX, Melo JV, Daley GQ. Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336. Blood. 2002;100:1068\u20131071.","DOI":"10.1182\/blood.V100.3.1068"},{"key":"2019111704475189600_R40","doi-asserted-by":"crossref","unstructured":"Klejman A, Rushen L, Morrione A, Slupianek A, Skorski T. Phosphatidylinositol-3 kinase inhibitors enhance the anti-leukemia effect of STI571. Oncogene. 2002;21:5868\u20135876.","DOI":"10.1038\/sj.onc.1205724"}],"container-title":["Hematology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2005\/1\/118\/644978\/118.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/hematology\/article-pdf\/2005\/1\/118\/644978\/118.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T06:39:43Z","timestamp":1626763183000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/hematology\/article\/2005\/1\/118\/19247\/Treatment-of-Philadelphia-ChromosomePositive-Acute"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,1,1]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,1,1]]}},"URL":"https:\/\/doi.org\/10.1182\/asheducation-2005.1.118","relation":{},"ISSN":["1520-4391","1520-4383"],"issn-type":[{"value":"1520-4391","type":"print"},{"value":"1520-4383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,1,1]]}}}