The effect of prior exposure to imatinib on transplant-related mortality

Center for Hematologic Malignancies, Oregon Health & Science University, Portland, OR 97239, USA. deininge@ohsu.edu

BACKGROUND AND OBJECTIVES: Imatinib is an effective treatment for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, relapse is common in patients with advanced or high risk disease. Such patients may be eligible for allogeneic stem cell transplantation (SCT), raising the question whether imatinib therapy may compromise the outcome of subsequent SCT. DESIGN AND METHODS: We retrospectively analyzed 70 patients with CML and 21 with Ph+ ALL who had received imatinib prior to SCT. Data were retrieved by directly contacting centers. Multivariate analysis was used to define factors associated with major outcomes (engraftment, graft-versus-host disease, relapse, non-relapse mortality) in addition to descriptive statistics. For the CML patients major outcomes were compared with those of historical controls drawn from the EBMT registry. RESULTS: At SCT, 44% of CML patients were in accelerated phase or blast crisis and 40% of ALL patients had active disease compared to 84% and 95% prior to imatinib. At 24 months, estimated transplant-related mortality was 44% and estimated relapse mortality 24%. Factors associated with shorter overall and progression-free survival were advanced disease at SCT and a female donor/male recipient pairing. No unusual organ toxicities were observed. Compared to historical controls, prior imatinib treatment did not influence overall survival, progression-free survival or non-relapse mortality, while there was a trend towards higher relapse mortality and significantly less chronic graft-versus-host disease. INTERPRETATION AND CONCLUSIONS: Within the limits of a heterogeneous and relatively small cohort of patients, we found no evidence that imatinib negatively affects major outcomes after SCT, suggesting that imatinib prior to SCT is safe.

This article has been cited by other articles:

				R. Hehlmann and S. Saussele Treatment of chronic myeloid leukemia in blast crisis Haematologica, December 1, 2008; 93(12): 1765 - 1769. [Full Text] [PDF]

				I. Iacobucci, A. Lonetti, D. Cilloni, F. Messa, A. Ferrari, R. Zuntini, S. Ferrari, E. Ottaviani, F. Arruga, S. Paolini, et al. Identification of different Ikaros cDNA transcripts in Philadelphia-positive adult acute lymphoblastic leukemia by a high-throughput capillary electrophoresis sizing method Haematologica, December 1, 2008; 93(12): 1814 - 1821. [Abstract] [Full Text] [PDF]

				P. Kebriaei, M. A. Detry, S. Giralt, A. Carrasco-Yalan, A. Anagnostopoulos, D. Couriel, I. F. Khouri, P. Anderlini, C. Hosing, A. Alousi, et al. Long-term follow-up of allogeneic hematopoietic stem-cell transplantation with reduced-intensity conditioning for patients with chronic myeloid leukemia Blood, November 1, 2007; 110(9): 3456 - 3462. [Abstract] [Full Text] [PDF]

				J. M. Goldman How I treat chronic myeloid leukemia in the imatinib era Blood, October 15, 2007; 110(8): 2828 - 2837. [Abstract] [Full Text] [PDF]

				V. G. Oehler, T. Gooley, D. S. Snyder, L. Johnston, A. Lin, C. C. Cummings, S. Chu, R. Bhatia, S. J. Forman, R. S. Negrin, et al. The effects of imatinib mesylate treatment before allogeneic transplantation for chronic myeloid leukemia Blood, February 15, 2007; 109(4): 1782 - 1789. [Abstract] [Full Text] [PDF]

				J. P. Radich The Biology of CML Blast Crisis Hematology, January 1, 2007; 2007(1): 384 - 391. [Abstract] [Full Text] [PDF]

				M. Baccarani, G. Saglio, J. Goldman, A. Hochhaus, B. Simonsson, F. Appelbaum, J. Apperley, F. Cervantes, J. Cortes, M. Deininger, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet Blood, September 15, 2006; 108(6): 1809 - 1820. [Abstract] [Full Text] [PDF]