Selection of unrelated bone marrow donors: does the current procedure warrant complete MHC class II identity?

Bone marrow transplantation from unrelated donors is being used increasingly for the treatment of patients with leukemia and several other hematologic disorders. Selection of unrelated bone marrow donors currently relies on serological HLA identity and negative mixed lymphocyte reactions between donor/recipient pairs. As serological HLA-DP typing is not feasible, we used the HLA-DPB1 oligonucleotide typing method to investigate whether the current selection procedure can guarantee complete MHC class II identity. In 40 consecutive patients, one third (62/193) serologically HLA-A, -B, -C, -DR and -DQ identical donors were found to be MLC negative with a relative response below 5%. HLA-DPB1 oligonucleotide typing of these MLC negative donors revealed that again only one third (20/62) was also identical for DP with their presumptive recipients. In the majority of pairs a disparity in graft-versus-host direction or in host-versus-graft direction of at least one allele was seen. These data indicate that in spite of the strict MLC criteria used, the current procedure did not warrant complete MHC class II identity. This implies that oligotyping for DPB1 can improve matching and should be introduced for typing of volunteers. We speculate that DP differences may contribute to the higher incidence of graft-versus-host disease or graft rejection in unrelated transplants.