Clinical Outcomes of HLA-DPB1 Mismatches in 10/10 HLA-Matched Donor-Recipient Pairs Undergoing Allogeneic Stem Cell Transplant

Abstract

Matching for HLA-DPB1 lowers relapse risk in allogeneic hematopoietic stem cell transplantation (ASCT), but this locus is not in linkage disequilibrium with the remainder of the HLA genes, making matching more difficult. Recent studies have suggested that after classifying HLA-DPB1 mismatches based on T-cell epitope group, avoiding non-permissive mismatches leads to improved survival. We tested this hypothesis in our patient population. We conducted a retrospective analysis of 78 patients who underwent ASCT at the Mayo Clinic 1/1/2008 - 12/21/2010. Patients with unrelated volunteer donors were matched for HLA-A, B, C, DRB1 and DQB1 loci (10/10) at the allele level without consideration of the HLA-DPB1 locus. Patient and donor HLA-DPB1 genotyping was performed by reverse SSO typing and the ImMunoGeneTics/HLA (IMGT/HLA) T-cell epitope matching algorithm was used to determine mismatch status as permissive or non-permissive. Of 78 donor recipient pairs, there were 13 HLA-DPB1 matches, 42 permissive mismatches, and 23 non-permissive mismatches (10 in the graft-vs-host [GvH] direction, 13 in the host-vs-graft [HvG] direction). In a univariate analysis, when matches and permissive mismatches were combined into a group and compared to non-permissive mismatch, there was no significant difference in overall survival (p=0.31), relapse (p=0.79), or neutrophil or platelet engraftment (p=0.23 and p=0.99, respectively). No significant difference was observed in acute graft-vs-host disease (aGVHD; p=0.25) or grade II-IV aGVHD (p=0.62) among the matched, permissive mismatched, and non-permissive mismatched groups. The permissive mismatched group showed an increase in chronic GVHD (cGVHD) over the matched and the non-permissive mismatched groups that neared significance (p=0.052). In univariate analyses, for non-permissive mismatches, the GvH mismatch direction trended toward reduced survival (p=0.26), increased relapse (p=0.13), increased aGVHD (p=0.064), and increased cGVHD (p=0.22). We did not identify any significant differences in survival, relapse, engraftment, or acute or chronic GVHD among the patients with HLA-DPB1 donor matches, permissive mismatches, and non-permissive mismatches, although our study was limited by small sample size. Further work from large databases is necessary to fully understand the impact on clinical outcomes of HLA-DPB1 mismatches.