1. Tyrosine kinase inhibitor prophylaxis after transplant for Philadelphia chromosome-positive acute lymphoblastic leukemia.
- Author
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Akahoshi Y, Nishiwaki S, Mizuta S, Ohashi K, Uchida N, Tanaka M, Fukuda T, Ozawa Y, Takahashi S, Onizuka M, Shiratori S, Nakamae H, Kanda Y, Ichinohe T, Atsuta Y, and Kako S
- Subjects
- Adolescent, Adult, Aged, Combined Modality Therapy, Dasatinib administration & dosage, Dasatinib pharmacology, Female, Fusion Proteins, bcr-abl drug effects, Humans, Imatinib Mesylate administration & dosage, Imatinib Mesylate pharmacology, Male, Middle Aged, Neoplasm, Residual, Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Protein Kinase Inhibitors pharmacology, Remission Induction, Retrospective Studies, Transplantation, Homologous, Treatment Outcome, Young Adult, Fusion Proteins, bcr-abl genetics, Hematopoietic Stem Cell Transplantation methods, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Protein Kinase Inhibitors administration & dosage
- Abstract
Tyrosine kinase inhibitor (TKI) administration after allogeneic hematopoietic stem cell transplantation (HSCT) may carry a survival benefit in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Therefore, we investigated whether TKI prophylaxis for negative-minimal residual disease (MRD) after HSCT would improve patient outcomes in this nationwide retrospective cohort study. We included patients with Ph+ ALL who underwent their first allogeneic HSCT between 2001 and 2016, received TKI before HSCT, and achieved negative-MRD status within 180 days after HSCT. Of 850 patients for inclusion, 50 patients received TKI prophylaxis, mostly imatinib or dasatinib (median dose: 400 mg with imatinib and 40 mg with dasatinib). In a multivariate analysis, disease status at HSCT was the sole risk factor for relapse (hazard ratio, 3.58; P < .001 for positive-MRD with complete remission [CR] and hazard ratio, 6.13; P < .001 for active disease). TKI prophylaxis was not associated with a decreased risk of relapse or superior overall survival in either the whole cohort or in the analysis limited to negative-MRD or positive-MRD with CR1 at HSCT. Meanwhile, TKI prophylaxis limited to dasatinib might be associated with a decreased risk of relapse (hazard ratio, 0.34; P = .140), unlike imatinib. Alternative strategies using new-generation TKI for high-risk patients are warranted to improve the outcomes after allogeneic HSCT., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Published
- 2019
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