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Application of MHC microsatellite analysis in donor-recipient matching for unrelated bone marrow transplantation

Matching of the Major Histocompatibility Complex (MHC) of the donor and recipient is the most important factor in the outcome of allogeneic bone marrow transplantation (alloBMT). The potential use of microsatellite markers in the identification of unrelated donor-recipient pairs identical for the entire MHC has been proposed. Twenty patients who underwent alloBMT for treatment of various hematologic malignancies were retrospectively studied. Fifteen of them received transplant from an unrelated donor (HLA-A, B, DRB1 and DQB1 matched), while for the remaining 5 patients, donor was a parent (HLA-A, B, DRB1 and DQB1 matched in 2 cases ; HLA-B allele mismatched in one case ; HLA-B and DRB1 allele mismatched in 2 cases). All pairs were tested for 12 HLA microsatellites (D6S1014, D6S265, D6S273, D6S2793, D6S291, D6S2927, D6S2939, MICA, MIB, TNFa, TNFb and TNFd). Analysis was performed using electrophoresis on a polyacrylamide gel in an ALFexpress sequencer (Pharmacia Biotech). According to the percentage of allele matching, microsatellite loci were divided in 3 groups: microsatellites with high matching level (>80%, D6S2927, MICA, MIB and TNFb), intermediate matching level (50-80%, D6S1014, D6S273 and TNFd), and low matching level (<50%, D6S265, D6S2793, D6S291, D6S2939 and TNFa). This was expected since the level of matching is proportional to the distance between microsatellites and HLA loci, their linkage disequilibrium and level of microsatellite polymorphism. Association of matching level and degree of GvHD could not be determined since 12 patients (60%) had GvHD grade 3 or higher, and out of the remaining 6 patients, 2 showed signs of transplant rejection and disease relapse. A larger group of patients is necessary to obtain conclusive results about the role of microsatellites in better definition of unrelated donors.

MHC microsatellites; unrelated bone marrow transplantation

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