Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation–related imatinib failure

E Jabbour, J Cortes, HM Kantarjian, S Giralt, D Jones… - Blood, 2006 - ashpublications.org
E Jabbour, J Cortes, HM Kantarjian, S Giralt, D Jones, R Jones, F Giles, BS Andersson…
Blood, 2006ashpublications.org
Resistance to imatinib mesylate is an emerging problem in the treatment of chronic myeloid
leukemia (CML), often associated with point mutations in the Bcr-Abl kinase domain.
Outcome of patients with such mutations after allogeneic stem cell transplantation (Allo-SCT)
is unknown. Ten imatinib-resistant patients with Bcr-Abl kinase mutations received a
transplant: 9 had CML (3 in chronic phase, 4 in accelerated phase, and 2 in blast phase)
and 1 had Philadelphia-positive acute lymphocytic leukemia (ALL). Patients harbored 9 …
Abstract
Resistance to imatinib mesylate is an emerging problem in the treatment of chronic myeloid leukemia (CML), often associated with point mutations in the Bcr-Abl kinase domain. Outcome of patients with such mutations after allogeneic stem cell transplantation (Allo-SCT) is unknown. Ten imatinib-resistant patients with Bcr-Abl kinase mutations received a transplant: 9 had CML (3 in chronic phase, 4 in accelerated phase, and 2 in blast phase) and 1 had Philadelphia-positive acute lymphocytic leukemia (ALL). Patients harbored 9 different protein kinase mutations (T315I mutation, n = 2). Preparative regimens were ablative (n = 7) and nonablative (n = 3). All patients engrafted; there were no treatment-related deaths. Disease response was complete molecular (CMR; n = 7), major molecular (n = 2), and no response (n = 1). Three patients (mutations Q252H, E255K, and T315I) died of relapse after Allo-SCT. Seven patients are alive (6 in CMR) for a median of 19 months. Allo-SCT remains an important salvage option for patients who develop resistance to imatinib through Bcr-Abl mutations.
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