Abstract
Since the introduction of imatinib mesylate, the role of allogeneic hematopoietic cell transplantation (allo-HCT) for CML has essentially been reserved for patients with advanced disease or imatinib resistance. In addition, there have been concerns regarding imatinib associated cardiac toxicity. We investigated the outcome of 61 patients with CML who received a myeloablative allo-HCT at the University of Minnesota between 1999 and 2006. The median age at HCT was 38.4 (range; 6.9–56.9) years. Thirty-seven patients were in first chronic phase and twenty-four patients in a second chronic or accelerated phase at the time of HCT. Twenty-six patients received imatinib therapy before or after HCT, and thirty-five patients either never received imatinib (n=32) or received it only at the time of relapse after HCT (n=3). OS and relapse-free survival (RFS) at 2 years was 69 and 55% for the imatinib group, and 57 and 49% for the non-imatinib group (P=0.57 and 0.95, respectively). There was no difference in the risk of relapse at 2 years between the groups. Symptomatic cardiac toxicity at 1 year was reported in three imatinib group (12%) and two non-imatinib group (6%) patients (P=0.44). Thus, patients treated with imatinib either before or after myeloablative allo-HCT had no increase in cardiac toxicity.
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References
Heisterkamp N, Stam K, Groffen J, de Klein A, Grosveld G . Structural organization of the bcr gene and its role in the Ph+ translocation. Nature 1985; 315: 758–761.
Lugo TG, Pendergast AM, Muller AJ, Witte ON . Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science 1990; 247: 1079–1082.
Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006; 355: 2408–2417.
Kantarjian HM, Talpaz M, O’Brien S, Jones D, Giles F, Garcia-Manero G et al. Survival benefit with imatinib mesylate versus interferon-alpha-based regimens in newly diagnosed chronic-phase chronic myelogenous leukemia. Blood 2006; 108: 835–1840.
Roy L, Guilhot J, Krahnke T, Guerci-Bresler A, Druker BJ, Larson RA et al. Survival advantage from imatinib compared with the combination interferon-alpha plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials. Blood 2006; 108: 1478–1484.
Kerkela R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 2006; 12: 908–916.
Fischer T, Reifenrath C, Hess GR, Corsetti MT, Kreil S, Beck J et al. Safety and efficacy of STI-571 (imatinib mesylate) in patients with bcr/abl-positive chronic myelogenous leukemia (CML) after autologous peripheral blood stem cell transplantation (PBSCT). Leukemia 2002; 16: 1220–1228.
Sawyers CL, Hochhaus A, Feldman E, Goldman JM, Miller CB, Ottmann OG et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood 2002; 99: 3530–3539.
Sohn SK, Kim JG, Kim DH, Lee KB . Cardiac morbidity in advanced chronic myelogenous leukaemia patients treated by successive allogeneic stem cell transplantation with busulphan/cyclophosphamide conditioning after imatinib mesylate administration. Br J Haematol 2003; 121: 469–472.
Cohen MH, Johnson JR, Pazdur R . US Food and Drug Administration Drug Approval Summary: conversion of imatinib mesylate (STI571; Gleevec) tablets from accelerated approval to full approval. Clin Cancer Res 2005; 11: 12–29.
Gambacorti-Passerini C, Tornaghi L, Franceschino A, Piazza R, Corneo G, Pogliani E . In reply to ‘Cardiotoxicity of the cancer therapeutic agent imatinib mesylate’. Nat Med 2007; 13: 13–14; author reply 15–16.
Hatfield A, Owen S, Pilot PR . In reply to ‘Cardiotoxicity of the cancer therapeutic agent imatinib mesylate’. Nat Med 2007; 13: 13; author reply 15–16.
Atallah E, Durand JB, Kantarjian H, Cortes J . Congestive heart failure is a rare event in patients receiving imatinib therapy. Blood 2007; 110: 1233–1237.
Orzan F, Brusca A, Conte MR, Presbitero P, Figliomeni MC . Severe coronary artery disease after radiation therapy of the chest and mediastinum: clinical presentation and treatment. Br Heart J 1993; 69: 496–500.
Morishita E, Nakao S, Asakura H, Jokaji H, Saito M, Uotani C et al. Hypercoagulability and high lipoprotein(a) levels in patients with aplastic anemia receiving cyclosporine. Blood Coagul Fibrinolysis 1996; 7: 609–614.
Deininger M, Schleuning M, Greinix H, Sayer HG, Fischer T, Martinez J et al. The effect of prior exposure to imatinib on transplant-related mortality. Haematologica 2006; 91: 452–459.
Giralt SA, Arora M, Goldman JM, Lee SJ, Maziarz RT, McCarthy PL et al. Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia. Br J Haematol 2007; 137: 461–467.
Oehler VG, Gooley T, Snyder DS, Johnston L, Lin A, Cummings CC et al. The effects of imatinib mesylate treatment before allogeneic transplantation for chronic myeloid leukemia. Blood 2007; 109: 1782–1789.
Zaucha JM, Prejzner W, Giebel S, Gooley TA, Szatkowski D, Kalwak K et al. Imatinib therapy prior to myeloablative allogeneic stem cell transplantation. Bone Marrow Transplant 2005; 36: 417–424.
Seggewiss R, Lore K, Greiner E, Magnusson MK, Price DA, Douek DC et al. Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner. Blood 2005; 105: 2473–2479.
Appel S, Balabanov S, Brummendorf TH, Brossart P . Effects of imatinib on normal hematopoiesis and immune activation. Stem Cells 2005; 23: 1082–1088.
Carpenter PA, Snyder DS, Flowers ME, Sanders JE, Gooley TA, Martin PJ et al. Prophylactic administration of imatinib after hematopoietic cell transplantation for high-risk Philadelphia chromosome-positive leukemia. Blood 2007; 109: 2791–2793.
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This work was supported by the Children's Cancer Research Fund (CCRF).
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Burke, M., Trotz, B., Luo, X. et al. Imatinib use either pre- or post-allogeneic hematopoietic cell transplantation (allo-HCT) does not increase cardiac toxicity in chronic myelogenous leukemia patients. Bone Marrow Transplant 44, 169–174 (2009). https://doi.org/10.1038/bmt.2008.441
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DOI: https://doi.org/10.1038/bmt.2008.441
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