Graft-versus-Host Disease-Free, Relapse-Free Survival after Allogeneic Stem Cell Transplantation for Myelodysplastic Syndrome

Biol Blood Marrow Transplant. 2019 Jan;25(1):63-72. doi: 10.1016/j.bbmt.2018.08.004. Epub 2018 Aug 10.

Abstract

Graft-versus-host disease-free, relapse-free survival (GRFS) is a composite endpoint that measures survival free of relapse or significant morbidity after allogeneic hematopoietic stem cell transplantation (HSCT). Consecutive adult patients (N = 324) who received HSCT with fludarabine and busulfan-based conditioning for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia evolved from MDS were retrospectively analyzed. One-year and 3-year GRFS rates were 47.8% and 34.5%, respectively. Three fixed factors (circulating blast > 3%, high cytogenetic risk, and high comorbidity index) and 2 factors (which are) modifiable by clinicians (myeloablative conditioning [MAC] and low-dose [<7.5 mg/kg] antithymocyte globulin [ATG]) were independent factors for poor GRFS. Based on these 5 factors, 3 groups (3-year GRFS: 64.9% in low risk, 33.6% in intermediate risk, and 6.6% in high risk; P < .001) were identified. Fixed factor-adjusted GRFS in patients receiving reduced-intensity conditioning (RIC) plus high-dose ATG (≥7.5 mg/kg) was superior (P < .001) to those receiving MAC and/or low-dose ATG. Favorable influences of RIC plus ATG ≥ 7.5 mg/kg were evident in the low-risk group defined by fixed factors (3-year GRFS, 38.9% versus 4.4%; P < .001) but were not evident in the high-risk group (3-year GRFS, .0% versus 5.3%; P = .678). Conclusively, this study suggests that risk-adapted selection of conditioning intensity and ATG could improve qualified HSCT outcomes.

Keywords: Antithymocyte globulin; GVHD-free; Hematopoietic stem cell transplantation; Myelodysplastic syndrome; Reduced-intensity conditioning; Relapse-free survival.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Allografts
  • Antilymphocyte Serum / administration & dosage
  • Busulfan / administration & dosage
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / mortality*
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / mortality*
  • Myelodysplastic Syndromes / therapy*
  • Retrospective Studies
  • Risk Factors
  • Survival Rate
  • Transplantation Conditioning*
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives

Substances

  • Antilymphocyte Serum
  • Vidarabine
  • Busulfan
  • fludarabine