High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation.
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.
Lee
Stephanie J
SJ
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. sjlee@fhcrc.org
Klein
John
J
Haagenson
Michael
M
Baxter-Lowe
Lee Ann
LA
Confer
Dennis L
DL
Eapen
Mary
M
Fernandez-Vina
Marcelo
M
Flomenberg
Neal
N
Horowitz
Mary
M
Hurley
Carolyn K
CK
Noreen
Harriet
H
Oudshoorn
Machteld
M
Petersdorf
Effie
E
Setterholm
Michelle
M
Spellman
Stephen
S
Weisdorf
Daniel
D
Williams
Thomas M
TM
Anasetti
Claudio
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016026:Bone Marrow Transplantation / Q000379:methods / Q000401:mortality / Q000592:standards*; D002648:Child; D002675:Child, Preschool; D004247:DNA; D006680:HLA Antigens / Q000235:genetics*; D006648:Histocompatibility; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007223:Infant; D008875:Middle Aged; D012042:Registries; D012189:Retrospective Studies; D015996:Survival Rate; D014019:Tissue Donors; D016896:Treatment Outcome