Haploidentical and Matched Sibling Donor Hematopoietic Cell Transplantation for Patients with HLA-Homozygous Haplotypes

Biol Blood Marrow Transplant. 2016 Nov;22(11):2031-2037. doi: 10.1016/j.bbmt.2016.07.020. Epub 2016 Aug 1.

Abstract

More than 1% of the Japanese population has HLA-homozygous haplotypes. For patients with such haplotypes, HLA-haploidentical family members who have no HLA mismatch in the graft-versus-host direction are readily available donor candidates for hematopoietic cell transplantation (HCT). In this study, the outcomes of patients with homozygous HLA-A, -B, and -DRB1 antigens who received HCT without T cell depletion from a haploidentical related donor with mismatches in the host-versus-graft direction only (hetero-to-homo, n = 78) or from an HLA-matched sibling donor (MSD) (MSD-homo, n = 153) were compared with those in patients with heterozygous haplotypes who received HCT from an MSD (MSD-hetero, n = 7242). Transplant outcomes in the hetero-to-homo group were similar to those in the MSD-hetero group regarding neutrophil engraftment, grades III to IV acute graft-versus-host disease (aGVHD), nonrelapse mortality (NRM), relapse, and overall survival. On the other hand, the incidences of severe aGVHD and NRM in the MSD-homo group were significantly lower than those in the MSD-hetero group (grades III to IV aGVHD: aHR .50, P = .034; NRM: aHR .48, P = .004). In conclusion, patients with HLA-homozygous haplotypes achieved lower GVHD and NRM rates for MSD transplantation than those with HLA-heterozygous haplotypes. When an MSD or an appropriate alternative donor is not available for patients with HLA-homozygous haplotypes who need immediate transplantation, transplantation from a haploidentical donor without T cell depletion is a viable option, given the comparable transplant outcomes for hetero-to-homo HCT and MSD-hetero HCT.

Keywords: Donor selection; GVHD; HLA mismatch; HLA-homozygous haplotypes; Host-versus-graft direction; Overall survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Genotype
  • Graft Survival
  • Graft vs Host Disease / immunology
  • HLA Antigens*
  • Haplotypes*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Recurrence
  • Siblings*
  • Survival Analysis
  • Tissue Donors
  • Transplantation, Haploidentical
  • Treatment Outcome
  • Young Adult

Substances

  • HLA Antigens