MEASUREMENT OF CYTOTOXIC T-LYMPHOCYTE PRECURSOR FREQUENCIES REVEALS CRYPTIC HLA CLASS-I MISMATCHES IN THE CONTEXT OF UNRELATED DONOR BONE-MARROW TRANSPLANTATION

Background. In this large, two-center study, 260 cytotoxic T lymphocyt e precursor (CTLp) frequency assays, performed to assess patient-donor compatibility, were analyzed in relation to the degree of HLA matchin g, Methods. While the tissue-typing techniques used at the Royal Postg raduate Medical School (RPMS) and Anthony Nolan Bone Marrow Trust (ANB MT) differ, the results of the analyses on the two sites are analogous , with high CTLp frequencies (>1:100,000) in 42% and 41% of recipient- donor pairs, respectively. Results, Recipient-donor combinations with class I mismatches and class II identity were associated with high CTL p frequencies (collectively 83% vs. 17% low CTLp). This correlation wa s not as strong in pairs where class II mismatches were demonstrated ( 61% high vs. 39% low). Despite using different matching procedures, th e RPMS and ANBMT both show that 32% of the ''perfectly'' matched pairs (i.e., where no mismatch was detected by any of the techniques used h ere) had high frequencies of recipient-specific CTLp, Conclusions. The failure of conventional methods to identify such a level of histoinco mpatibilities indicates that the CTLp? assay has an important role in the selection of unrelated donors for bone marrow transplantation.