title: Identification of a permissible HLA mismatch in hematopoietic stem cell transplantation.
abstract: In subjects mismatched in the HLA alleles C*03:03/C*03:04 no allogeneic cytotoxic T-lymphocyte responses are detected in vitro. Hematopoietic stem cell transplantation (HSCT) with unrelated donors (UDs) showed no association between the HLA-C allele mismatches (CAMMs) and adverse outcomes; antigen mismatches at this and mismatches other HLA loci are deleterious. The absence of effect of the CAMM may have resulted from the predominance of the mismatch C*03:03/C*03:04. Patients with hematologic malignancies receiving UD HSCT matched in 8/8 and 7/8 HLA alleles were examined. Transplants mismatched in HLA-C antigens or mismatched in HLA-A, -B, or -DRB1 presented significant differences (P < .0001) in mortality (hazard ratio [HR] = 1.37, 1.30), disease-free survival (HR = 1.33, 1.27), treatment-related mortality (HR = 1.54, 1.54), and grade 3-4 acute graft-versus-host disease (HR = 1.49, 1.77) compared with the 8/8 group; transplants mismatched in other CAMMs had similar outcomes with HR ranging from 1.34 to 172 for these endpoints. The C*03:03/C*03:04 mismatched and the 8/8 matched groups had identical outcomes (HR ranging from 0.96-1.05). The previous finding that CAMMs do not associate with adverse outcomes is explained by the predominance (69%) of the mismatch C*03:03/03:04 in this group that is better tolerated than other HLA mismatches.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA;
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Fernandez-Viña
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Haagenson
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Aljurf
authors.forename: Medhat
authors.initials: M
authors.lastname: Askar
authors.forename: Minoo
authors.initials: M
authors.lastname: Battiwalla
authors.forename: Lee-Ann
authors.initials: LA
authors.lastname: Baxter-Lowe
authors.forename: James
authors.initials: J
authors.lastname: Gajewski
authors.forename: Ann A
authors.initials: AA
authors.lastname: Jakubowski
authors.forename: Susana
authors.initials: S
authors.lastname: Marino
authors.forename: Machteld
authors.initials: M
authors.lastname: Oudshoorn
authors.forename: Steven G E
authors.initials: SG
authors.lastname: Marsh
authors.forename: Effie W
authors.initials: EW
authors.lastname: Petersdorf
authors.forename: Kirk
authors.initials: K
authors.lastname: Schultz
authors.forename: E Victoria
authors.initials: EV
authors.lastname: Turner
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
authors.forename: Ann
authors.initials: A
authors.lastname: Woolfrey
authors.forename: John
authors.initials: J
authors.lastname: Umejiego
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Spellman
authors.forename: Michelle
authors.initials: M
authors.lastname: Setterholm
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology; D019337:Hematologic Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007223:Infant; D008875:Middle Aged; D015999:Multivariate Analysis; D015995:Prevalence; D012307:Risk Factors; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D015236:HLA-C Antigens