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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4576-4583.
Prepublished online as a Blood First Edition Paper on September 4, 2007; DOI 10.1182/blood-2007-06-097386.
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TRANSPLANTATION
High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation
Stephanie J. Lee1,
John Klein2,
Michael Haagenson3,
Lee Ann Baxter-Lowe4,
Dennis L. Confer5,
Mary Eapen2,
Marcelo Fernandez-Vina6,
Neal Flomenberg7,
Mary Horowitz2,
Carolyn K. Hurley8,
Harriet Noreen9,
Machteld Oudshoorn10,
Effie Petersdorf1,
Michelle Setterholm5,
Stephen Spellman5,
Daniel Weisdorf11,
Thomas M. Williams12, and
Claudio Anasetti13
1 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
2 Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee;
3 Center for International Blood and Marrow Transplant Research, Minneapolis, MN;
4 Department of Surgery, University of California, San Francisco;
5 National Marrow Donor Program, Minneapolis, MN;
6 M. D. Anderson Cancer Center, Houston, TX;
7 Thomas Jefferson University Hospital, Philadelphia, PA;
8 Department of Oncology, Georgetown University Medical Center, Washington, DC;
9 Immunology/Histocompatibility Laboratory, University of Minnesota Medical Center, Fairview;
10 Europdonor Foundation, Leiden, the Netherlands;
11 Blood and Marrow Transplantation (BMT) Program, University of Minnesota, Minneapolis;
12 Department of Pathology, University of New Mexico, Albuquerque; and
13 H. Lee Moffitt Cancer Center, Tampa, FL
The relative importance of various human leukocyte antigen (HLA) loci and the resolution level at which they are matched has not been fully defined for unrelated donor transplantation. To address this question, National Marrow Donor Program data from 3857 transplantations performed from 1988 to 2003 in the United States were analyzed. Patient-donor pairs were fully typed for HLA-A, -B, -C, -DRB1, -DQB1, -DQA1, -DPB1, and -DPA1 alleles. High-resolution DNA matching for HLA-A, -B, -C, and -DRB1 (8/8 match) was the minimum level of matching associated with the highest survival. A single mismatch detected by low- or high-resolution DNA testing at HLA-A, -B, -C or -DRB1 (7/8 match) was associated with higher mortality (relative risk, 1.25; 95% CI, 1.13-1.38; P < .001) and 1-year survival of 43% compared with 52% for 8/8 matched pairs. Single mismatches at HLA-B or HLA-C appear better tolerated than mismatches at HLA-A or HLA-DRB1. Mismatching at 2 or more loci compounded the risk. Mismatching at HLA-DP or -DQ loci and donor factors other than HLA type were not associated with survival. In multivariate modeling, patient age, race, disease stage, and cytomegalovirus status were as predictive of survival as donor HLA matching. High-resolution DNA matching for HLA-A, -B, -C, and -DRB1 alleles is associated with higher rates of survival.

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