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.
MeSH terms
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Adult
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Benzamides
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Blast Crisis / genetics
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Blast Crisis / metabolism
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Blast Crisis / mortality
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Blast Crisis / therapy
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Disease-Free Survival
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Drug Resistance, Neoplasm / drug effects
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Drug Resistance, Neoplasm / genetics*
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Female
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Fusion Proteins, bcr-abl / antagonists & inhibitors
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Fusion Proteins, bcr-abl / genetics*
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Fusion Proteins, bcr-abl / metabolism
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Graft Survival / drug effects
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Graft Survival / genetics
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Humans
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Imatinib Mesylate
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
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Male
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Middle Aged
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Piperazines / administration & dosage
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Point Mutation*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
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Protein Kinase Inhibitors / administration & dosage
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Pyrimidines / administration & dosage
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Recurrence
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Salvage Therapy
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Stem Cell Transplantation*
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Transplantation, Homologous
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Treatment Outcome
Substances
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Benzamides
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Piperazines
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Protein Kinase Inhibitors
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Pyrimidines
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Imatinib Mesylate
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Fusion Proteins, bcr-abl