Novel Indicators of Transplant Outcomes for PhALL: Current Molecular-Relapse-Free Survival

Hideki Nakasone, Shinichi Kako, Takayoshi Tachibana, Masatsugu Tanaka, Makoto Onizuka, Satoshi Takahashi, Akira Yokota, Shin Ichiro Fujiwara, Toru Sakura, Emiko Sakaida, Shin Fujisawa, Rie Yamazaki, Moritaka Gotoh, Maki Hagihara, Nobuyuki Aotsuka, Nobuhiro Tsukada, Yoshihiro Hatta, Hiroaki Shimizu, Kensuke Usuki, Reiko WatanabeTakehiko Mori, Shingo Yano, Heiwa Kanamori, Yoshinobu Kanda

Research output: Contribution to journalArticlepeer-review

Abstract

Molecular relapse after allogeneic hematopoietic cell transplantation (allo-HCT) has been thought to predict clinical relapse in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia (PhALL). Tyrosine kinase inhibitor (TKI) administration after allo-HCT may dynamically change the status from molecular relapse to molecular remission, but these state changes cannot be accurately represented by conventional survival indicators such as relapse-free survival, where events are usually considered irreversible. We aimed to develop novel indicators of transplant outcomes for allo-HCT recipients with PhALL and to visualize current molecular-relapse-free survival (CMRFS) and current on-TKI status (CTKI), treating molecular relapse or TKI administration after allo-HCT as a reversible event. We retrospectively analyzed 286 patients with PhALL who received allo-HCT between 2000 and 2016 in order to develop the indicators. CMRFS was defined as the probability of molecular remission without clinical relapse or death at any time after allo-HCT. Similarly, CTKI was defined as the probability of TKI administration without clinical relapse or death at any time after allo-HCT. The 1- and 5-year CMRFS rates were 67% and 59%, respectively, whereas the 1- and 5-year conventional molecular relapse-free survival rates were 42% and 37%. The 1- and 5-year CTKI rates were 14% and 8%, respectively. In a post hoc analysis focusing on patients who had achieved a molecular complete remission within 6 weeks (n = 201), the 5-year CMRFS rate (71%) was similar to the 5-year conventional molecular relapse-free survival (molRFS) rate (70%) in the non-TKI group. On the other hand, the 5-year CMRFS rate in the TKI group was 61%, whereas the 5-year conventional molRFS rate was only 38%. CMRFS and CTKI might become useful indicators of transplant success in terms of survival, leukemia-free status, and treatment-free status at any time point. Future extension of these survival models to other clinical situations is warranted.

Original languageEnglish
JournalTransplantation and Cellular Therapy
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • Current molecular-relapse-free survival (CMRFS)
  • Current on-TKI status (CTKI)
  • Philadelphia chromosome–positive acute lymphoblastic leukemia (PhALL)
  • Tyrosine kinase inhibitors (TKI)

ASJC Scopus subject areas

  • Hematology
  • Transplantation
  • Immunology and Allergy
  • Cell Biology
  • Molecular Medicine
  • Medicine(all)

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