Clinical outcomes of HLA-DPB1 mismatches in 10/10 HLA-matched unrelated donor-recipient pairs undergoing allogeneic stem cell transplant

Eur J Haematol. 2017 Sep;99(3):275-282. doi: 10.1111/ejh.12916. Epub 2017 Jul 21.

Abstract

Objective: HLA-DPB1 matching may impact allogeneic hematopoietic stem cell transplantation (ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA-DPB1 mismatches based on T-cell epitope, avoiding non-permissive mismatches may impact survival. We tested this hypothesis at a single academic institution.

Methods: Retrospective HLA-DPB1 genotyping was performed on 153 adult patients who underwent ASCT and unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 loci (10/10). Using the ImMunoGeneTics/HLA T-cell epitope matching algorithm, mismatch status was classified as permissive or non-permissive.

Results: Of 153 donor-recipient pairs, 22 (14.4%) were HLA-DPB1 matches, 64 (42.8%) permissive mismatches, and 67 (43.8%) non-permissive mismatches. DPB1 mismatch increased risk of chronic graft-versus-host disease (cGVHD; RR 2.89 [1.19-9.53], P=.016) compared with DPB1-matched transplants, but there were no differences in overall mortality, risk of relapse, or acute GVHD (aGVHD). Combining matches and permissive mismatches and comparing to non-permissive mismatches, there was no significant difference in overall survival or relapse; however, patients receiving non-permissive mismatched transplants experienced greater risk of aGVHD overall and severe aGVHD (RR 1.66 [1.13-2.44], P=.010 and RR 1.97 [1.10-3.59], P=.024, respectively).

Conclusion: In this single-center study, HLA-DPB1 matching influenced outcomes of patients undergoing ASCT for hematologic malignancy.

Keywords: bone marrow transplantation; transplantation.

MeSH terms

  • Adolescent
  • Adult
  • Alleles*
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control
  • HLA Antigens / genetics*
  • HLA-DP beta-Chains / genetics*
  • Hematologic Neoplasms / complications
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Histocompatibility Testing
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocyte Depletion
  • Male
  • Middle Aged
  • Mortality
  • Outcome Assessment, Health Care
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Unrelated Donors*
  • Young Adult

Substances

  • HLA Antigens
  • HLA-DP beta-Chains
  • HLA-DPB1 antigen