Dose-Reduced Versus Standard Conditioning Followed by Allogeneic Stem-Cell Transplantation for Patients With Myelodysplastic Syndrome: A Prospective Randomized Phase III Study of the EBMT (RICMAC Trial)

J Clin Oncol. 2017 Jul 1;35(19):2157-2164. doi: 10.1200/JCO.2016.70.7349. Epub 2017 May 2.

Abstract

Purpose To compare a reduced-intensity conditioning regimen (RIC) with a myeloablative conditioning regimen (MAC) before allogeneic transplantation in patients with myelodysplastic syndrome (MDS) within a randomized trial. Patients and Methods Within the European Society of Blood and Marrow Transplantation, we conducted a prospective, multicenter, open-label, randomized phase III trial that compared a busulfan-based RIC with MAC in patients with MDS or secondary acute myeloid leukemia. A total of 129 patients were enrolled from 18 centers. Patients were randomly assigned in a 1:1 ratio and were stratified according to donor, age, and blast count. Results Engraftment was comparable between both groups. The CI of acute graft-versus-host disease II to IV was 32.3% after RIC and 37.5% after MAC ( P = .35). The CI of chronic graft-versus-host disease was 61.6% after RIC and 64.7% after MAC ( P = .76). The CI of nonrelapse mortality after 1 year was 17% (95% CI, 8% to 26%) after RIC and 25% (95% CI, 15% to 36%) after MAC ( P = .29). The CI of relapse at 2 years was 17% (95% CI, 8% to 26%) after RIC and 15% (95% CI, 6% to 24%) after MAC ( P = .6), which resulted in a 2-year relapse-free survival and overall survival of 62% (95% CI, 50% to 74%) and 76% (95% CI, 66% to 87%), respectively, after RIC, and 58% (95% CI, 46% to 71%) and 63% (95% CI, 51% to 75%), respectively, after MAC ( P = .58 and P = .08, respectively). Conclusion This prospective, randomized trial of the European Society of Blood and Marrow Transplantation provides evidence that RIC resulted in at least a 2-year relapse-free survival and overall survival similar to MAC in patients with MDS or secondary acute myeloid leukemia.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Busulfan / administration & dosage
  • Cyclophosphamide / administration & dosage
  • Dose-Response Relationship, Drug
  • Female
  • Graft vs Host Disease / etiology
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / surgery
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / surgery
  • Myelodysplastic Syndromes / therapy*
  • Stem Cell Transplantation / adverse effects
  • Stem Cell Transplantation / methods*
  • Transplantation Conditioning / adverse effects
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Young Adult

Substances

  • Cyclophosphamide
  • Vidarabine
  • Busulfan
  • fludarabine