Refractory Graft-Versus-Host Disease–Free, Relapse-Free Survival as an Accurate and Easy-to-Calculate Endpoint to Assess the Long-Term Transplant Success

Koji Kawamura, Hideki Nakasone, Saiko Kurosawa, Kazuki Yoshimura, Yukiko Misaki, Ayumi Gomyo, Jin Hayakawa, Masaharu Tamaki, Yu Akahoshi, Machiko Kusuda, Kazuaki Kameda, Hidenori Wada, Yuko Ishihara, Miki Sato, Kiriko Terasako-Saito, Misato Kikuchi, Shun ichi Kimura, Aki Tanihara, Shinichi Kako, Heiwa KanamoriTakehiko Mori, Satoshi Takahashi, Shuichi Taniguchi, Yoshiko Atsuta, Yoshinobu Kanda

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


The aim of this study was to develop a new composite endpoint that accurately reflects the long-term success of allogeneic hematopoietic stem cell transplantation (allo-HSCT), as the conventional graft-versus-host disease (GVHD)–free, relapse-free survival (GRFS) overestimates the impact of GVHD. First, we validated current GRFS (cGRFS), which recently was proposed as a more accurate endpoint of long-term transplant success. cGRFS was defined as survival without disease relapse/progression or active chronic GVHD at a given time after allo-HSCT, calculated using 2 distinct methods: a linear combination of a Kaplan-Meier estimates approach and a multistate modelling approach. Next, we developed a new composite endpoint, refractory GRFS (rGRFS). rGRFS was calculated similarly to conventional GRFS treating grade III to IV acute GVHD, chronic GVHD requiring systemic treatment, and disease relapse/progression as events, except that GVHD that resolved and did not require systemic treatment at the last evaluation was excluded as an event in rGRFS. The 2 cGRFS curves obtained using 2 different approaches were superimposed and both were superior to that of conventional GRFS, reflecting the proportion of patients with resolved chronic GVHD. Finally, the curves of cGRFS and rGRFS overlapped after the first 2 years of post-transplant follow-up. These results suggest that cGRFS and rGRFS more accurately reflect transplant success than conventional GRFS. Especially, rGRFS can be more easily calculated than cGRFS and analyzed with widely used statistical approaches, whereas cGRFS more accurately represents the burden of GVHD-related morbidity in the first 2 years after transplantation.

Original languageEnglish
Pages (from-to)1521-1526
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Issue number7
Publication statusPublished - 2018 Jul


  • Acute GVHD
  • Allogeneic hematopoietic stem cell transplantation
  • Chronic GVHD
  • Endpoint
  • Quality of life

ASJC Scopus subject areas

  • Hematology
  • Transplantation


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