STRATEGIES FOR DETERMINING HLA COMPATIBILITY IN RELATED DONOR BONE-MARROW TRANSPLANTATION

Background. Although HLA identity between donor and recipient is no lo nger an absolute requirement for bone marrow transplantation, knowledg e of the degree of HLA compatibility is necessary for determining the induction and immunosuppression regimen to be used. In cases of relate d donor transplantation, KLA compatibility may be assessed by defining the HLA phenotypes at the allele level using high-resolution, DNA-bas ed typing methods or by determining the genotypes of the patient and p otential donor from the HLA phenotypes, ascertained by low-resolution typing, of their family members. Methods. We developed an algorithm th at can be used to assess the relative costs of these two approaches, W e applied population frequencies for HLA-DR alleles to this algorithm to determine at what; cost per test ratio for high-resolution:low-reso lution testing the costs of the two approaches are equal. Results. In transplants involving a sibling pair who have the same HLA-A, -B, and -DR antigens, these values are 1.16-1.83 for African-Americans and 1.2 3-1.97 for Caucasians, depending on the relatives available for testin g With a slight increase in the resolution level achieved with DR, ant igen testing, the range of values becomes 1.10-1.74. We also estimated that the probability that two antigenically identical siblings have i dentical HLA-DRB1 alleles is >99% for both African-Americans and Cauca sians, A review of 615 cases from our transplant program showed that a ll of 192 pairs of antigenically identical patients and sibling donors were genotypically or allelically identical, indicating that this est imate is valid. Conclusions. Transplant programs can apply these algor ithms to determine the most cost-effective scheme for histocompatibili ty testing.