title: Multiple mismatches at the low expression HLA loci DP, DQ, and DRB3/4/5 associate with adverse outcomes in hematopoietic stem cell transplantation.
abstract: A single mismatch in highly expressed HLA-A, -B, -C, and -DRB1 loci (HEL) is associated with worse outcomes in hematopoietic stem cell transplantation, while less is known about the cumulative impact of mismatches in the lesser expressed HLA loci DRB3/4/5, DQ, and DP (LEL). We studied whether accumulation of LEL mismatches is associated with deleterious effects in 3853 unrelated donor transplants stratified according to number of matches in the HEL. In the 8/8 matched HEL group, LEL mismatches were not associated with any adverse outcome. Mismatches at HLA-DRB1 were associated with occurrence of multiple LEL mismatches. In the 7/8 HEL group, patients with 3 or more LEL mismatches scored in the graft-versus-host vector had a significantly higher risk of mortality (1.45 and 1.43) and transplant-related mortality (1.68 and 1.54) than the subgroups with 0 or 1 LEL mismatches. No single LEL locus had a more pronounced effect on clinical outcome. Three or more LEL mismatches are associated with lower survival after 7/8 HEL matched transplantation. Prospective evaluation of matching for HLA-DRB3/4/5, -DQ, and -DP loci is warranted to reduce posttransplant risks in donor-recipient pairs matched for 7/8 HEL.
authors.affiliation: Department of Pathology, Stanford Medical School Blood Center, 3373 Hillview Ave, Palo Alto, CA 94304, USA. marcelof@stanford.edu
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Fernández-Viña
authors.forename: John P
authors.initials: JP
authors.lastname: Klein
authors.forename: Michael
authors.initials: M
authors.lastname: Haagenson
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Spellman
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
authors.forename: Harriet
authors.initials: H
authors.lastname: Noreen
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Baxter-Lowe
authors.forename: Pedro
authors.initials: P
authors.lastname: Cano
authors.forename: Neal
authors.initials: N
authors.lastname: Flomenberg
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Confer
authors.forename: Mary M
authors.initials: MM
authors.lastname: Horowitz
authors.forename: Machteld
authors.initials: M
authors.lastname: Oudshoorn
authors.forename: Effie W
authors.initials: EW
authors.lastname: Petersdorf
authors.forename: Michelle
authors.initials: M
authors.lastname: Setterholm
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
mesh_terms: D000328:Adult; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000401:mortality; D006682:HLA-DP Antigens / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology*; D059806:HLA-DR beta-Chains / Q000276:immunology*; D059826:HLA-DRB3 Chains / Q000276:immunology; D059845:HLA-DRB4 Chains / Q000276:immunology; D059847:HLA-DRB5 Chains / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006648:Histocompatibility; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D059806:HLA-DR beta-Chains; D059826:HLA-DRB3 Chains; D059845:HLA-DRB4 Chains; D059847:HLA-DRB5 Chains