title: HLA-C antigen mismatch is associated with worse outcome in unrelated donor peripheral blood stem cell transplantation.
abstract: The association between HLA matching and outcome in unrelated-donor peripheral blood stem cell (PBSC) transplantation has not yet been established. In the present study, a total of 1933 unrelated donor-recipient pairs who underwent PBSC transplantation between 1999 and 2006 for acute myelogenous leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia and received high-resolution HLA typing for HLA-A, -B, -C, -DRB1, -DQA1, and -DQB1 were included in the analysis. Outcomes were compared between HLA-matched and HLA-mismatched pairs, adjusting for patient and transplant characteristics. Matching for HLA-A, -B, -C, and -DRB1 alleles (8/8 match) was associated with better survival at 1 year compared with 7/8 HLA-matched pairs (56% vs 47%). Using 8/8 HLA-matched patients as the baseline (n = 1243), HLA-C antigen mismatches (n = 189) were statistically significantly associated with lower leukemia-free survival (relative risk [RR], 1.36; 95% confidence interval [CI], 1.13-1.64; P = .0010), and increased risk for mortality (RR, 1.41; 95% CI, 1.16-1.70; P = .0005), treatment-related mortality (RR, 1.61; 95% CI, 1.25-2.08; P = .0002), and grade III-IV graft-versus-host disease (RR, 1.98; 95% CI, 1.50-2.62; P < .0001). HLA-B antigen or allele mismatching was associated with an increased risk for acute GVHD grade III-IV. No statistically significant differences in outcome were observed for HLA-C allele (n = 61), HLA-A antigen/allele (n = 136), HLA-DRB1 allele (n = 39), or HLA-DQ antigen/allele (n = 114) mismatches compared with 8/8 HLA-matched pairs. HLA mismatch was not associated with relapse or chronic GVHD. HLA-C antigen-mismatched unrelated PBSC donors were associated with worse outcomes compared with 8/8 HLA-matched donors. The study's limited power due to small sample size precludes conclusions about other mismatches.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. awoolfre@fhcrc.org
authors.forename: Ann
authors.initials: A
authors.lastname: Woolfrey
authors.forename: John P
authors.initials: JP
authors.lastname: Klein
authors.forename: Michael
authors.initials: M
authors.lastname: Haagenson
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.forename: Effie
authors.initials: E
authors.lastname: Petersdorf
authors.forename: Machteld
authors.initials: M
authors.lastname: Oudshoorn
authors.forename: James
authors.initials: J
authors.lastname: Gajewski
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hale
authors.forename: John
authors.initials: J
authors.lastname: Horan
authors.forename: Minoo
authors.initials: M
authors.lastname: Battiwalla
authors.forename: Susana R
authors.initials: SR
authors.lastname: Marino
authors.forename: Michelle
authors.initials: M
authors.lastname: Setterholm
authors.forename: Olle
authors.initials: O
authors.lastname: Ringden
authors.forename: Carolyn
authors.initials: C
authors.lastname: Hurley
authors.forename: Neal
authors.initials: N
authors.lastname: Flomenberg
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez-Vina
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000483:Alleles; D001782:Blood Donors; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D059811:HLA-DRB1 Chains; D006648:Histocompatibility / Q000235:genetics / Q000276:immunology; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology* / Q000401:mortality*; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D014180:Transplantation; D016896:Treatment Outcome
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains