Submitted February 6, 2006
Accepted March 26, 2006
Allogeneic stem cell transplantation for patients with
chronic myeloid leukemia and acute lymphocytic leukemia
after BCR-ABL kinase mutation-related imatinib failure
Elias Jabbour, Jorge Cortes, Hagop M. Kantarjian, Sergio Giralt, Dan Jones, Roy Jones, Francis Giles, Borje S Andersson, Richard Champlin, and Marcos de Lima*
Departments of Blood and Marrow Transplantation, University of Texas MD Anderson Cancer Center
Leukemia, University of Texas MD Anderson Cancer Center
Leukemia, University of Texas M. D. Anderson Cancer Center
Departments of Blood and Marrow Transplantation, University of Texas M. D. Anderson Cancer Center
Hematopathology, University of Texas MD Anderson cancer Center
* Corresponding author; email: mdelima{at}mdanderson.org.
Resistance to imatinib 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 transplantation (Allo-SCT) is unknown. Ten imatinib-resistant patients with Bcr-abl kinase mutations received transplantation: nine had CML (three in chronic phase, four in accelerated phase, and two in blast phase) and one had Philadelphia-positive ALL. Patients harbored nine different protein kinase mutations (T315I mutation, n=2). Preparative regimens were ablative (n=7) and non-ablative (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 (six 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.
