title: Limits of HLA mismatching in unrelated hematopoietic cell transplantation.
abstract: 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.
authors.affiliation: Division of Clinical Research, D4-100 Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA. epetersd@fhcrc.org
authors.forename: Effie W
authors.initials: EW
authors.lastname: Petersdorf
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.forename: Ted
authors.initials: T
authors.lastname: Gooley
authors.forename: Jerald
authors.initials: J
authors.lastname: Radich
authors.forename: Mari
authors.initials: M
authors.lastname: Malkki
authors.forename: Ann
authors.initials: A
authors.lastname: Woolfrey
authors.forename: Anajane
authors.initials: A
authors.lastname: Smith
authors.forename: Eric
authors.initials: E
authors.lastname: Mickelson
authors.forename: John A
authors.initials: JA
authors.lastname: Hansen
mesh_terms: 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
chemical_list: D006680:HLA Antigens; D019653:Myeloablative Agonists