OR43 Frequency of HLA DPA1 and DPB1 mismatching in a population of 1199 pairs of presumed HLA identical sibling transplant pairs

Abstract

Aim The ideal graft source for allogeneic hematopoietic stem cell transplantation (HCT) is an HLA-identical matched sibling (MSD). The Blood and Marrow Transplant Clinical Trials Network recommends that family donors be HLA-A and -B typed at intermediate or higher resolution and HLA-DRB1 typed at high resolution by DNA-based methods as a minimum requirement. Where possible, familial haplotypes should be assigned to establish presumptive high-resolution match identity between the donor and recipient (additionally HLA-C and DQB1 may be considered). Extended typing at additional HLA loci including DPB1 is not commonly performed. Results from unrelated donor HCT studies suggest that mismatches at HLA-DPB1 increase the risk of acute graft versus host disease. Due to the genetic distance from the other classical loci crossover events may lead to mismatching at DPB1 in the MSD setting and therefore may ultimately play a role in transplant outcomes. Methods A cohort of 1199 presumed MSD pairs, from 55 centers, collected by the CIBMTR Research Repository from 2007 to 2015 were analyzed. All pairs were reported to the CIBMTR as HLA identical siblings and received a transplant for either AML (44%), ALL (24%), MDS (26%) and 6% other diseases. The median patient age was 52, 59% were male, 86% received PBSC and 14% BM. To determine the crossover frequency the subjects were typed by targeted exon NGS of exons 2 and 3 for both Class I and Class II yielding G group or better results, at HLA-A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPA1 and DPB1. Results The majority (97.25%) of MSD pairs were identical at all loci tested. A small subset (2.75%) of the pairs contained a mismatch impacting either DPA1, DPB1 or both. The majority of the 33 mismatches, 26 (78.79%) were DPB1, 6 (18.18%) included both DPA1 and DPB1 and 1 (3.03%) only DPA1. Analysis of the T-cell-epitope groups found that 28% of the DPB1 mismatches were not permissive. All were presumed crossover events, but family typing was not available to confirm. Six (18%) of the DPB1 mismatches included a homozygous recipient with a heterozygous donor suggesting a potential loss of heterozygosity. Conclusion The mismatch frequency at the DP loci in MSD pairs was relatively low at 2.75% and 28% were not TCE permissive. The impact of DP mismatching on MSD HCT outcomes are unclear and warrant further study.