Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome.

Abstract

Outcome of unrelated donor marrow transplantation is influenced by donor-recipient matching for HLA. Prior studies assessing the effects of mismatches at specific HLA loci have yielded conflicting results. The importance of high-resolution matching for all HLA loci has also not been established. We therefore examined the effects of HLA matching (low or high resolution or both) on engraftment, graft-versus-host disease (GVHD), and mortality in 1874 donor-recipient pairs retrospectively typed at high resolution for HLA-A, -B, -C, -DRB1, -DQ, and -DP. Mismatches at HLA-A, -B, -C, and -DRB1 each had similar adverse effects on mortality. Only HLA-A mismatches demonstrated significant adverse effects on GVHD. These adverse effects on outcome were more evident in transplants with low-resolution versus only high-resolution mismatches. Mismatches for HLA-DQ or -DP did not significantly affect outcome. When high-resolution mismatches at HLA-A, -B, -C, and -DRB1 were considered together, adverse effects on survival and GVHD were observed. We therefore conclude that matching for HLA-C should be incorporated into algorithms for unrelated donor selection. High-resolution mismatches at HLA-A, -B, -C, and -DRB1 adversely affect outcome, but less so than low-resolution mismatches. When clinical circumstances allow, high-resolution class I typing may help optimize donor selection and improve outcome.

• Authors: Neal Flomenberg, Lee Ann Baxter-Lowe, Dennis Confer, Marcelo Fernandez-Vina, Alexandra Filipovich, Mary Horowitz, Carolyn Hurley, Craig Kollman, Claudio Anasetti, Harriet Noreen, Ann Begovich, William Hildebrand, Effie Petersdorf, Barbara Schmeckpeper, Michelle Setterholm, Elizabeth Trachtenberg, Thomas Williams, Edmond Yunis, Daniel Weisdorf
• Journal: Blood (Blood) Vol. 104 Issue 7 Pg. 1923-30 (Oct 01 2004) ISSN: 0006-4971 [Print] United States
• PMID: 15191952 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• HLA Antigens
• HLA-A Antigens
• HLA-B Antigens
• HLA-C Antigens
• HLA-DP Antigens
• HLA-DQ Antigens
• HLA-DR Antigens
• HLA-DRB1 Chains
• Histocompatibility Antigens Class I
• Histocompatibility Antigens Class II

Topics

• Adult
• Alleles
• Bone Marrow Transplantation (methods)
• Graft Survival
• Graft vs Host Disease (etiology)
• HLA Antigens (chemistry)
• HLA-A Antigens (chemistry)
• HLA-B Antigens (chemistry)
• HLA-C Antigens (chemistry, immunology)
• HLA-DP Antigens (chemistry)
• HLA-DQ Antigens (chemistry)
• HLA-DR Antigens (chemistry)
• HLA-DRB1 Chains
• Hematopoietic Stem Cells (immunology)
• Histocompatibility
• Histocompatibility Antigens Class I (genetics)
• Histocompatibility Antigens Class II (genetics)
• Histocompatibility Testing
• Humans
• Leukemia (therapy)
• Time Factors
• Tissue Donors
• Treatment Outcome