Stopping tyrosine kinase inhibitors started after allogeneic HCT in patients with Philadelphia chromosome-positive leukemia

Hideki Nakasone, Shinichi Kako, Takehiko Mori, Satoshi Takahashi, Makoto Onizuka, Shin ichiro Fujiwara, Toru Sakura, Emiko Sakaida, Akira Yokota, Nobuyuki Aotsuka, Maki Hagihara, Nobuhiro Tsukada, Yoshihiro Hatta, Kensuke Usuki, Reiko Watanabe, Moritaka Gotoh, Shin Fujisawa, Shingo Yano, Heiwa Kanamori, Shinichiro OkamotoYoshinobu Kanda

Research output: Contribution to journalArticlepeer-review


For patients with Philadelphia chromosome (Ph)-positive leukemia, there is no consensus regarding how long tyrosine kinase inhibitors (TKI) should be given or whether TKI could be stopped if TKI is administrated after allogeneic hematopoietic cell transplantation (allo-HCT). We analyzed relapse-free survival (RFS) in 92 allo-HCT patients who received TKI for >3 months after allo-HCT, and aimed to develop a novel indicator, called as current TKI- & relapse-free (cTRFree) achievement. TKI after allo-HCT was started as planned in 39 patients, based on measurable residual disease (MRD) in 53 at a median of 152 days after allo-HCT. There was no difference in post-TKI RFS between the planned and MRD-based starting groups (P = 0.69). Second-generation TKIs were associated with superior RFS in Ph-positive acute leukemia (HR 2.71, P = 0.031). TKI was stopped before relapse in 48 patients. Stopping TKI as a time-dependent covariate was not associated with subsequent hematological relapse (HR 1.18, P = 0.72). In the TKI-stop group, TKI administration for >6 months tended to be associated with superior RFS (HR = 0.30, P = 0.08). As an indicator of transplant success, cTRFree was 35% 5 years after starting TKI. TKI could be stopped for recipients with sustained undetectable MRD. However, further prospective studies will be required to establish clinical recommendations.

Original languageEnglish
Pages (from-to)1402-1412
Number of pages11
JournalBone Marrow Transplantation
Issue number6
Publication statusPublished - 2021 Jun
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Transplantation


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