Impact of Molecular HLA Matching for Allogeneic Stem Cell Transplantation from Unrelated Donors.

Two hundred and fourteen unrelated donor transplants (HSCT) using peripheral blood (N=60) or marrow (N=154) as a stem cell source have been performed in Switzerland since 1990. All transplants were coordinated by the Swiss bone marrow donor registry and were performed at 4 different institutions. Median age was 28 (1–61) years, and 132 (62%) patients were male. Twenty-four patients with malignancy underwent transplants with reduced intensity conditioning regimens. T-cell depletion was performed in 45 patients. Patients had CML (62), AML (53), ALL (36), MDS/MPS (31), lymphoid malignancies (14), acquired or congenital aplastic anemia (11), or other inherited disorders (7). Sixty-two patients with AML, ALL or CML were transplanted at an early disease stage, i.e. CR1 or 1st chronic phase, the remainder with more advanced disease. All donor/recipient pairs underwent high resolution HLA typing in the LNRH, the Swiss national reference laboratory for histocompatibility in Geneva. Donor/recipient pairs were HLA-A, -B, -C, -DRB1/B3/B5, -DQB1 matched (130), or were mismatched at the HLA-A or B (10), HLA-C (29) HLA-DR (14), HLA-DQ (16) or at multiple (15) loci. Median follow-up of surviving patients was 34 months. Survival probabilities (± 95% CI) at 2 years were, in decreasing order 62 ± 9% for recipients of HLA 10/10 matched transplants, 46 ± 26% with DQB1 mismatch, 42 ± 20% with HLA-C mismatch, 30 ± 27% with HLA-DRB1 or DRB3 mismatch, 15 ± 26% with HLA-A or B mismatch and 13 ± 18% with multiple mismatches, p<0.0001. In multivariate analysis HLA compatibility, as defined by molecular typing, was the variable most significantly associated with survival and treatment-related mortality.

Multivariate analysis for survival

Unrelated donor transplantation is increasingly used in Switzerland to treat a variety of disorders. Long term survival in recipients of transplants from HLA-A/B/C/DR/DQ-matched donors (10/10) is comparable to that achieved with genotypically identical sibling donors. Single mismatches at HLA-C or DQB1 loci may be more acceptable than A, B or DR-incompatibilities which are associated with decreased survival. Without a suitable donor, alternative methods to unrelated donor HSCT should be considered.