BONE-MARROW TRANSPLANTATION USING UNRELATED AND FAMILY RELATED DONORS- THE IMPACT OF HLA-C DISPARITY

The clinical outcomes of unrelated and of family related allogeneic bo ne marrow transplantation (BMT) were correlated with HLA disparity in a study in which molecular phenotyping of HLA-C was performed for unre lated donor-recipient pairs. The study included 30 patients who underw ent BMT from unrelated donors and 43 patients who underwent BMT from f amily related donors. The unrelated group included 14 full match pairs , 12 class-I-C (molecular HLA-C) mismatched pairs, and 4 haploidentica l pairs. The family related group included 9 full match pairs, 19 clas s-I mismatched pairs, and 15 haploidentical pairs. In the unrelated BM T group, the transplant-related complications of mortality, graft-vers us-host disease (GVHD), and graft rejection, were significantly higher in molecular HLA-C mismatched than matched patients (67% vs 14% P < 0 .02; 50% vs 7%, P < 0.02; 42% vs 0, P < 0.02). The actuarial survival and the disease free survival (DFS) at 18 months was better for molecu lar HLA-C matched than for HLA-C mismatched unrelated transplants: 33% vs 18% (P = 0.065, NS), and 29% vs 16%, respectively, For the family related BMT group, the actuarial survival at 18 months was significant ly higher for patients who were fully matched compared to those who we re class-I mismatched, or those who were haploidentical pairs: 67%, 37 %, and 13% respectively (P < 0.02). The actuarial DFS at 18 months of patients who mere fully matched and of those who were class-I mismatch ed was similar, and better than that of haploidentical patients 45%,37 % (NS) and 13% respectively (P < 0.045). A lower incidence of transpla nt-related mortality occurred in class-I mismatched, family related (3 7%) than in locus-C mismatched unrelated patients (67%), and no differ ence was observed in the fully matched famiy related and unrelated pat ients. We conclude that a mismatch in locus C may be detrimental to BM T outcome and should therefore be included as a risk factor in the rou tine pre-BMT HLA phenotyping.