Early cardiotoxicity in post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis after HLA-haploidentical hematopoietic stem cell transplantation

Int J Hematol. 2025 Aug;122(2):247-256. doi: 10.1007/s12185-025-03970-w. Epub 2025 Mar 23.

Abstract

Introduction: Post-transplant cyclophosphamide (PTCy)-based prophylaxis for graft-versus-host disease (GVHD) is widely used in HLA-haploidentical hematopoietic cell transplantation (haplo-HCT). One of the major drawbacks of PTCy is the risk of rare but potentially lethal cardiotoxicity, which prompted the development of regimens with reduced doses of PTCy.

Methods: We retrospectively compared the incidence of early cardiotoxicity with standard-dose of PTCy (cyclophosphamide 50 mg/kg/day for 2 days, PTCy100) versus reduced-dose (40 mg/kg/day for 2 days, PTCy80). In total, 179 patients underwent PTCy-based haplo-HCT, including PTCy100 (n = 111) and PTCy80 (n = 68).

Results: The PTCy80 group included significantly more elderly patients, patients who received reduced-intensity conditioning, and patients with a history of HCT than the PTCy100 group. Nine eligible patients (5.0%) experienced severe cardiotoxicity. The incidence of severe cardiotoxicity did not differ significant between PTCy80 and PTCy100 (4.4% vs. 5.4%; p = 1). The incidence of fatal cardiotoxicity was lower with PTCy80, but the small size may have prevented the difference from reaching statistical significance.

Conclusion: Reducing the cyclophosphamide dose in PTCy-based GVHD prophylaxis may lower the risk of fatal cardiotoxicity without significantly altering the overall incidence of severe cardiotoxicity.

Keywords: Cardiotoxicity; Graft-versus host disease; North Japan hematology study group; Post-transplant cyclophosphamide.

MeSH terms

  • Adult
  • Aged
  • Cardiotoxicity* / etiology
  • Cyclophosphamide* / administration & dosage
  • Cyclophosphamide* / adverse effects
  • Cyclophosphamide* / therapeutic use
  • Female
  • Graft vs Host Disease* / etiology
  • Graft vs Host Disease* / prevention & control
  • HLA Antigens / genetics
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Retrospective Studies
  • Transplantation Conditioning
  • Transplantation, Haploidentical* / adverse effects

Substances

  • Cyclophosphamide
  • HLA Antigens