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When the first allogeneic bone marrow transplants in humans was attempted, little was known of the major histocompatibility complex (HLA) and its role in ensuring success of the graft. Therefore, many of the early attempts resulted in failure. During the 1970s just a small number of alleles were detected serologically and the mixed lymphocyte reaction (MLR) served as a surrogate for class II matching, the DR series of alleles not being formally serologically defined until 1978. Nevertheless, selection of nuclear family members who were two HLA haplotype matched became possible using serology and the MLR and transplant successes were reported.

The breakthrough in technology was undoubtedly the introduction of DNA techniques, particularly DNA sequencing. This enabled fully matched unrelated individuals to be found as potential bone marrow donors. Genetic phasing or haplotyping of unrelated donors who are found on bone marrow registries has remained elusive until recently. The development of individual chromosome sequencing will permit haplotype matching in the absence of family studies and will expedite studies aimed at identifying other genes which are important matching factors.

AIM: The aim of this review is to outline the technological advances that have been made in HLA genotyping over the last 50 years. The progress from serology to DNA sequence as part of the matching algorithm is one of the reasons clinical results have improved so much during this period. This review outlines the DNA techniques that have been utilised for this purpose, concluding with a discussion of the value of haplotype matching in unrelated donor transplants, where the donor has been sourced from a bone marrow registry. Haplotype matching represents one of the last remaining hurdles to be overcome  in unrelated donor bone marrow transplants.