Impact of high-resolution matching in allogeneic unrelated donor stem cell transplantation in Switzerland

It is currently unknown what degree of human leukocyte antigen (HLA)-mismatching is acceptable in unrelated donor hematopoietic stem cell transplantation (UD-HSCT). Mismatches at some loci maybe more permissive than others. We have analyzed the effect of high-resolution HLA-matching on outcome of all 214 consecutive recipients of UD-HSCT carried out in Switzerland. All typing was by the Swiss reference laboratory. Donor-recipient pairs were HLA-10/10 matched (n = 130) or mismatched for either HLA-A/ -B/-DRB1/multiple loci (n = 33; (HLA-A/-B = 10); (-DRB1 = 8); (multiple = 15)); HLA-C (n = 29) or HLA-DQ/DRB3 (n = 22; (DQ = 16); (-DRB1 = 6)). The median follow-up was 32 months. Survival probabilities (+/- 95% confidence interval) at 3 years were 57 (+/- 10)% for recipients of HLA 10/10-matched transplants, 53 (+/- 22)% for recipients of HLA-DQ/-DRB3-mismatched transplants, 44 (+/- 20)% for recipients of HLA-C-mismatched transplants and 0% for recipients of transplants mismatched at HLA-A/-B/-DRB1/multiple loci (P < 0.0001). In multivariate analyses, HLA compatibility was the variable most significantly associated with survival and treatment-related mortality. We found important differences in survival in recipients of UD-HSCT with best results for transplants from 10/10 matched donors. Single mismatches at HLA-DQ/-DRB3 were well tolerated, mismatches at HLA-C had intermediate results and mismatches at HLA-A/-B/-DRB1/multiple loci resulted in poor survival.