Tyrosine kinase inhibitor prophylaxis after transplant for Philadelphia chromosome-positive acute lymphoblastic leukemia

the Adult Acute Lymphoblastic Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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.

Original languageEnglish
Pages (from-to)3255-3266
Number of pages12
JournalCancer Science
Volume110
Issue number10
DOIs
StatePublished - 1 Oct 2019
Externally publishedYes

Keywords

  • Philadelphia chromosome-positive acute lymphoblastic leukemia
  • dasatinib
  • imatinib
  • minimal residual disease
  • post-transplant tyrosine kinase inhibitor

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