Melphalan-based conditioning with post-transplant cyclophosphamide for peripheral blood stem cell transplantation: donor effect

Bone Marrow Transplant. 2025 May;60(5):625-631. doi: 10.1038/s41409-025-02523-3. Epub 2025 Feb 27.

Abstract

Fludarabine and melphalan (FM) conditioning offers effective disease control with an acceptable toxicity profile. Post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis has improved transplant outcomes. We retrospectively reviewed patients receiving FM-based transplants with PTCy at City of Hope. Of 248 patients included, 89 (35.9%) received hematopoietic cell transplant (HCT) from a matched related/unrelated donor (MRD/MUD), 118 (47.6%) from a haploidentical (HID) donor, and 49 (19.8%) from a mismatched unrelated donor (MMUD). There were no differences in acute and chronic GVHD based on donor type. The 2-year overall survival (OS) for patients receiving HID, MMUD, and MRD/MUD was 58%, 55%, and 70%; disease-free survival (DFS) was 52%, 48%, and 66%; and graft-versus-host/relapse-free survival (GRFS) were 48%, 40%, and 59%, respectively. OS, DFS, and GRFS were similar regardless of donor type on multivariable analysis. However, donor age ≥35 years was associated with lower OS and GRFS and higher 2-year non-relapse mortality (NRM) on multivariable analysis across all patients, regardless of donor type. FM with PTCy appears to produce similar outcomes between MRD/MUD, MMUD, and HID when adjusting for donors <35 years, and donor age seems to be the most important factor when selecting a donor with this regimen.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Cyclophosphamide* / administration & dosage
  • Cyclophosphamide* / pharmacology
  • Cyclophosphamide* / therapeutic use
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / prevention & control
  • Humans
  • Male
  • Melphalan* / administration & dosage
  • Melphalan* / pharmacology
  • Melphalan* / therapeutic use
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation* / methods
  • Retrospective Studies
  • Transplantation Conditioning* / methods
  • Unrelated Donors
  • Young Adult

Substances

  • Cyclophosphamide
  • Melphalan