Molecular techniques for typing unrelated marrow donors: potential impact of molecular typing disparity on donor...

HLA matching between a bone marrow recipient and donor is one of the major factors influencing transplant success. However, it is not possible to locate an HLA-identical donor for about 70% of patients who might benefit from bone marrow transplantation (BMT). New molecular biological methods for detection of HLA polymorphism currently provide an opportunity to improve HLA matching of unrelated donors as well as a research tool to investigate the relationship between HLA disparity and transplant complications. These molecular HLA typing methods include sequence-specific amplification, hybridization with oligonucleotide probes, heteroduplex formation and direct nucleotide sequencing. Molecular HLA typing is being utilized to address questions regarding the extent of HLA disparity between two unrelated individuals and the effect of HLA disparity that is not detected using conventional HLA typing methods. Accumulating data suggest some HLA disparities may be tolerated while others are very immunogenic. Use of more precise HLA typing may contribute to the success of future transplants utilizing alternative donors. A better understanding of the relationship between HLA disparity and transplant complications may make it possible to relax the stringency of donor matching to make BMT available to larger numbers of patients.