Risk-adapted GVHD prophylaxis with post-transplantation cyclophosphamide in adults after related, unrelated, and haploidentical transplantations

Eur J Haematol. 2018 May;100(5):395-402. doi: 10.1111/ejh.13030. Epub 2018 Mar 1.

Abstract

Introduction: Although a number of studies were published on the efficacy of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis, no large studies prospectively evaluated this strategy in related, unrelated, and haploidentical grafts.

Methods: In this study, GVHD prophylaxis for 57 matched bone marrow (MBM) grafts consisted of single-agent PTCy, for 88 matched PBSC grafts (MPBSC) consisted of PTCy, tacrolimus, and mycophenolate mofetil (MMF) 30 mg/kg, and for 55 mismatched grafts (MMGs) consisted of PTCy, tacrolimus and MMF 45 mg/kg.

Results: The study met the primary endpoint to demonstrate equivalent rates of acute GVHD grade II-IV (11%, 17%,19%, P = .46), III-IV (7%, 2%, 6%, P = .41), and moderate and severe chronic GVHD (22%, 11%, 15%, P = .23). There was also no differences in non-relapse mortality (11% vs 15% vs 17%, P = .75), overall survival (63% vs 71% vs 56%, P = .72), event-free-survival (51% vs 66% vs 48%, P = .32) for MBM, MPBSC, and MMG groups, respectively. Toxicity was comparable between groups except higher incidence of nephrotoxicity in combination arms (P = .0005) and higher incidence of graft failures in MMG group (P = .004).

Conclusion: The suggested risk-adapted PTCy-based prophylaxis is feasible and is associated with low GVHD incidence and mortality in all types of grafts. The study was registered on clinicaltrials.gov (NCT02294552).

Keywords: bone marrow transplantation; clinical trials.

MeSH terms

  • Adolescent
  • Adult
  • Cyclophosphamide / therapeutic use*
  • Female
  • Graft Survival
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / prevention & control*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Postoperative Care
  • Premedication
  • Tissue Donors
  • Transplantation Conditioning / adverse effects
  • Transplantation, Haploidentical
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Cyclophosphamide

Associated data

  • ClinicalTrials.gov/NCT02294552