Aim: HLA matching between allogenic hematopoietic stem cell transplant (HSCT) recipients and donors is a determinant for positive patient outcomes. Current NMDP guidelines suggest having allelic matches at HLA-A, -B, -C, and -DRB1 and to minimize mismatches at -DQB1 and -DRB3/4/5. Even with strong linkage disequilibrium between DRB1 and DRB3/4/5, mismatches between a potential donor and recipient at the DRB3/4/5 loci can occur. Historically, our clinicians have sought to mitigate Class I and Class II mismatches, with a bias towards 10/10 matching. Since the DRB3/4/5 locus was not intentionally factored in when matching potential donors and recipients, this retrospective study sought to determine the number of matched unrelated donors (MUD) allogenic HSCTs that included a DRB3/4/5 mismatch.
Method: High-resolution Next Generation Sequencing (NGS) of all potential donors and recipients was completed by our HLA lab. This information was used by the clinicians, along with HLA director guidance, to select the best match for allogenic HSCT. The number of 10/10 matches was tabulated and DRB3/4/5 mismatches were analyzed.
Results: A total of 175 allogenic HSCTs occurred during 2022-2023, with 124 of those being 10/10 matches. From among the 10/10 matched pairs, the table depicts donor-recipient genotypes where a DRB3/4/5 mismatch occurred. Bolded red alleles represent mismatched antigens. Bolded gold alleles share the same antigen group but are not in the same P group. Bolded green alleles are in the same P group. Empty boxes represent an absent second allele.
Conclusion: Historically conservative MUD HSCT matching by our clinicians has unintentionally led to few DRB3/4/5 mismatches. All of those mismatches have occurred at the allelic level with none at the antigen level. Due to the small number of mismatches, no outcome analysis was performed. However, the introduction of post-transplant cyclophosphamide therapy allows for an increase in mismatched donors, including at Class II; so it is likely that a greater number of mismatches will occur in the future.
