Nonmyeloablative HLA-haploidentical bone marrow transplantation with high-dose posttransplantation cyclophosphamide: effect of HLA disparity on outcome

Biol Blood Marrow Transplant. 2010 Apr;16(4):482-9. doi: 10.1016/j.bbmt.2009.11.011. Epub 2010 Jan 18.

Abstract

Although some reports have found an association between increasing HLA disparity between donor and recipient and fewer relapses after allogeneic blood or marrow transplantation (BMT), this potential benefit has been offset by more graft-versus-host disease (GVHD) and nonrelapse mortality (NRM). However, the type of GVHD prophylaxis might influence the balance between GVHD toxicity and relapse. The present study analyzed the impact of greater HLA disparity on outcomes of a specific platform for nonmyeloablative (NMA), HLA-haploidentical transplantation. A retrospective analysis was performed of 185 patients with hematologic malignancies enrolled in 3 similar trials of NMA, related donor, haploidentical BMT incorporating high-dose posttransplantation cyclophosphamide for GVHD prophylaxis. No significant association was found between the number of HLA mismatches (HLA-A, -B, -Cw, and -DRB1 combined) and risk of acute grade II-IV GVHD (hazard ratio [HR] = 0.89; P = .68 for 3-4 vs fewer antigen mismatches). More mismatching also had no detrimental effect on event-free survival (on multivariate analysis, HR = 0.60, P = .03 for 3-4 vs fewer antigen mismatches and HR = 0.55, P = .03 for 3-4 vs fewer allele mismatches). Thus, greater HLA disparity does not appear to worsen overall outcome after NMA haploidentical BMT with high-dose posttransplantation cyclophosphamide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bone Marrow Transplantation / immunology
  • Bone Marrow Transplantation / methods*
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage*
  • Disease-Free Survival
  • Female
  • Graft Rejection / genetics
  • Graft Rejection / immunology
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / immunology
  • HLA Antigens / genetics
  • HLA Antigens / immunology*
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / surgery*
  • Histocompatibility
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Infant
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Recurrence
  • Retrospective Studies
  • Transplantation Conditioning
  • Treatment Outcome
  • Young Adult

Substances

  • HLA Antigens
  • Immunosuppressive Agents
  • Cyclophosphamide