Identification of DPB1 Permissive Unrelated Donors Is Highly Likely

Abstract

HLA-DPB1 permissive matching based on T cell epitope (TCE) groups should be considered when selecting among equally matched HLA-A, -B, -C, -DRB1 unrelated hematopoietic stem cell donors to improve patient survival. Previous studies have defined 3 TCE groups based on functional assays of alloreactivity. Combinations of donor and recipient DPB1 alleles with low immunogenic potential identify permissive donors, who provide no increased risk of mortality compared with DPB1-matched donors. To determine the likelihood of identifying a DPB1 permissive-matched (includes both allele-matched and DPB1-permissive mismatched) unrelated donor for patients with high-resolution matches at 10/10 HLA-A, -B,- C, -DRB1, and -DQB1 in the Be The Match Registry, preliminary search requests from United States' transplant centers for 595 DPB1-typed patients were evaluated for existence of a DPB1 permissive-matched donor, identified either among already typed donors or by prospective DPB1 typing. The baseline DPB1 permissive match rate was 69% and improved to 80% after additional donor DPB1 typing (median, 4 donors per patient). When seeking a 10/10-matched, young (18- to 32-year-old) donor in the registry, the probability of finding a DPB1 permissive-matched donor started lower at 59% and improved to 70% after additional DPB1 testing. Our results show that most patients with a 10/10 match can find a DPB1 permissive-matched donor.

Chromosome Y–encoded antigens associate with acute graft-versus-host disease in sex-mismatched stem cell transplant

“…This is consistent with baseline likelihoods of finding HLA-DPB1 matches with productive 10/10 searches. 61 We found that HLA-DPB1 allele mismatching did not associate with acute GVHD (P , .92), whereas TCE mismatching did associate as expected (P , .038; 1-sided Fisher's exact test), leaving 56 out of 102 acute GVHD cases (55%) unaccounted for by mismatching at 6 HLA loci.…”

Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation

“…The National Marrow Donor Program also provides a Web-based application that incorporates the HLA-DPB1 TCE algorithm for transplant centers to search unrelated donors and cord blood units. 31 Although HLA-DPB1 non-PM was associated with an increased risk of grade 3-4 acute GVHD, it did not affect overall survival after UR-BMT in the current JMDP analysis. We speculate that the discrepancy in transplant outcomes associated with HLA-DPB1 TCE mismatching between Caucasian and Japanese patients might be partly attributed to ethnic backgrounds.…”

Selection of unrelated donors and cord blood units for hematopoietic cell transplantation: guidelines from the NMDP/CIBMTR

“…While allele matching at DPB1 is less frequent, identifying TCE permissive donors can be highly successful. 71 Direction of the mismatch If either the recipient or donor expresses only a single HLA allele at a locus (ie, is homozygous), then a unidirectional mismatch will occur. There are 2 types of unidirectional mismatches in HCT.…”