title: Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation-related imatinib failure.
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.
authors.affiliation: Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Roy
authors.initials: R
authors.lastname: Jones
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: Borje S
authors.initials: BS
authors.lastname: Andersson
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
mesh_terms: D000328:Adult; D001549:Benzamides; D001752:Blast Crisis / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage; D017354:Point Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D012008:Recurrence; D016879:Salvage Therapy; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl