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Previous Volume 345:1794-1800 December 20, 2001 Number 25 Next

	Full Text PDF Supplementary Material Editorial by Rubinstein, P. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Successful engraftment of hematopoietic stem cells from unrelated donors is influenced by disparities between the donor and recipient for HLA-A, B, and C alleles. Disparities between HLA sequence polymorphisms that are serologically detectable are termed antigen mismatches, whereas those that can be identified only by DNA-based typing methods are termed allele mismatches. Whether both kinds of polymorphisms are important in transplantation is not known. We tested the hypothesis that allele mismatches that are detectable only at the DNA level are less immunogenic than those that are serologically detectable and thereby are associated with a lower risk of graft failure after hematopoietic-cell transplantation.

Methods We used DNA sequencing to define the HLA-A, B, and C alleles in 471 patients who received bone marrow from unrelated donors for the treatment of chronic myeloid leukemia after myeloablative conditioning therapy. The odds ratios for graft failure were determined for recipients of transplants from donors with a single class I allele mismatch, a single class I antigen mismatch, or two or more class I mismatches, as compared with those with no mismatch.

Results A single HLA allele mismatch did not increase the risk of graft failure, whereas a single antigen mismatch significantly increased the risk. The risk was also increased if the recipient was HLA homozygous at the mismatched class I locus or if the donor had two or more class I mismatches.

Conclusions HLA class I antigen mismatches that are serologically detectable confer an enhanced risk of graft failure after hematopoietic-cell transplantation. Transplants from donors with a single class I allele mismatch that is not serologically detectable may be used without an increased risk of graft failure.

Source Information

From the Fred Hutchinson Cancer Research Center (E.W.P., J.A.H., P.J.M., A.W., M.M., T.G., B.S., E.M., C.A.), the University of Washington School of Medicine (E.W.P., J.A.H., P.J.M., A.W., C.A.), and the Seattle Cancer Care Alliance (A.S.) — all in Seattle.

Address reprint requests to Dr. Petersdorf at the Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, or at epetersd{at}fhcrc.org.

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