title: Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation.
abstract: Anti-HLA donor-specific Abs (DSAs) have been reported to be associated with graft failure in mismatched hematopoietic stem cell transplantation; however, their role in the development of graft failure in matched unrelated donor (MUD) transplantation remains unclear. We hypothesize that DSAs against a mismatched HLA-DPB1 locus is associated with graft failure in this setting. The presence of anti-HLA Abs before transplantation was determined prospectively in 592 MUD transplantation recipients using mixed-screen beads in a solid-phase fluorescent assay. DSA identification was performed using single-Ag beads containing the corresponding donor's HLA-mismatched Ags. Anti-HLA Abs were detected in 116 patients (19.6%), including 20 patients (3.4%) with anti-DPB1 Abs. Overall, graft failure occurred in 19 of 592 patients (3.2%), including 16 of 584 (2.7%) patients without anti-HLA Abs compared with 3 of 8 (37.5%) patients with DSA (P = .0014). In multivariate analysis, DSAs were the only factor highly associated with graft failure (P = .0001; odds ratio = 21.3). Anti-HLA allosensitization was higher overall in women than in men (30.8% vs 12.1%; P < .0001) and higher in women with 1 (P = .008) and 2 or more pregnancies (P = .0003) than in men. We conclude that the presence of anti-DPB1 DSAs is associated with graft failure in MUD hematopoietic stem cell transplantation.
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Ciurea
authors.forename: Peter F
authors.initials: PF
authors.lastname: Thall
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Sa A
authors.initials: SA
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: Pedro
authors.initials: P
authors.lastname: Cano
authors.forename: Fleur
authors.initials: F
authors.lastname: Aung
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rondon
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Molldrem
authors.forename: Martin
authors.initials: M
authors.lastname: Korbling
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.forename: Marcos
authors.initials: M
authors.lastname: de Lima
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez-Vina
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000378:metabolism* / Q000502:physiology; D000918:Antibody Specificity; D001788:Blood Grouping and Crossmatching; D002648:Child; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D000906:Antibodies; D006680:HLA Antigens