Limits of HLA mismatching in unrelated hematopoietic cell transplantation.
HLA matching between the donor and recipient improves the success of unrelated hematopoietic cell transplantation (HCT). Matched donors are available for only a minority of patients. Further information is needed to evaluate the limits of HLA mismatching. We examined the association of mortality with HLA-A, -B, -C, -DRB1, and -DQB1 mismatching in 948 patients who received a T-replete unrelated HCT for treatment of a marrow disorder. A single HLA allele or antigen mismatch was associated with increased mortality among patients with chronic myeloid leukemia (CML) within 2 years after diagnosis compared to patients with no HLA mismatch, but not among those with more advanced malignancy. In particular, a single HLA-C mismatch conferred increased risk of mortality compared to matches. There was a suggestion for increased mortality with multiple mismatches involving HLA-DQB1 compared to multiple mismatches not involving HLA-DQB1. Donors with a single HLA allele or antigen mismatch may be used for HCT when a fully matched donor is not available for patients with diseases that do not permit time for a lengthy search. Whenever possible, HLA-C mismatches should be avoided for patients with early stage CML, and HLA-DQB1 mismatches should be avoided for patients with multiple mismatches.
Petersdorf
Effie W
EW
Division of Clinical Research, D4-100 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA. epetersd@fhcrc.org
Anasetti
Claudio
C
Martin
Paul J
PJ
Gooley
Ted
T
Radich
Jerald
J
Malkki
Mari
M
Woolfrey
Ann
A
Smith
Anajane
A
Mickelson
Eric
E
Hansen
John A
JA
D000483:Alleles; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006648:Histocompatibility / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000628:therapy; D008297:Male; D019653:Myeloablative Agonists / Q000627:therapeutic use; D012306:Risk; D016019:Survival Analysis; D014181:Transplantation Immunology; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D006680:HLA Antigens; D019653:Myeloablative Agonists