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The role of the immunogenetics laboratory in marrow transplantation
1Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Wash.
Allogeneic marrow transplants from genotypically HLA-identical siblings have become lifesaving therapy for patients with various congenital and acquired diseases of the immune and hematopoietic systems. Unfortunately, less than 30% of patients in the United States have an HLA-identical sibling; therefore, many are denied the opportunity for potentially curative treatment for otherwise fatal conditions. The results of marrow transplantation from haploidentical family members who were partially compatible for nonshared haplotypes with the patients demonstrated the relevance of HLA compatibility for engraftment and graft-vs-host disease. These results have provided the rationale for using HLA-identical unrelated volunteers as marrow donors. The recent development of a national registry of volunteer bone marrow donors (the National Marrow Donor Program in the United States) has made it possible to access a centralized file of more than 260,000 HLA-typed volunteers. Marrow transplants from an unrelated donor have become feasible. However, our preliminary clinical experience clearly demonstrated an increase in the incidence and severity of graft-vs-host disease. It is likely that standard HLA typing techniques are not adequate to provide data for sufficient donor and recipient matching. It is possible that currently available molecular technology could be applied to HLA typing and donor matching to improve on clinical results.
Allogeneic marrow transplants from genotypically HLA-identical siblings have become lifesaving therapy for patients with various congenital and acquired diseases of the immune and hematopoietic systems. Unfortunately, less than 30% of patients in the United States have an HLA-identical sibling; therefore, many are denied the opportunity for potentially curative treatment for otherwise fatal conditions. The results of marrow transplantation from haploidentical family members who were partially compatible for nonshared haplotypes with the patients demonstrated the relevance of HLA compatibility for engraftment and graft-vs-host disease. These results have provided the rationale for using HLA-identical unrelated volunteers as marrow donors. The recent development of a national registry of volunteer bone marrow donors (the National Marrow Donor Program in the United States) has made it possible to access a centralized file of more than 260,000 HLA-typed volunteers. Marrow transplants from an unrelated donor have become feasible. However, our preliminary clinical experience clearly demonstrated an increase in the incidence and severity of graft-vs-host disease. It is likely that standard HLA typing techniques are not adequate to provide data for sufficient donor and recipient matching. It is possible that currently available molecular technology could be applied to HLA typing and donor matching to improve on clinical results.