title: The detection of donor-directed, HLA-specific alloantibodies in recipients of unrelated hematopoietic cell transplantation is predictive of graft failure.
abstract: Donor-directed human leukocyte antigen (HLA)-specific allo-antibodies (DSAs) cause graft failure in animal models of hematopoietic stem cell transplantation (HCT). Archived pretransplantation sera from graft failure patients (n = 37) and a matched case-control cohort (n = 78) were tested to evaluate the role of DSAs in unrelated donor HCT. Controls were matched for disease, disease status, graft type, patient age, and transplantation year. Patients had acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome; 98% received myeloablative conditioning regimens 100% received T-replete grafts, 97% received marrow, 95% HLA-mismatched, and 97% received calcineurin-based graft-versus-host disease prophylaxis. Among the 37 failed transplantations, 9 (24%) recipients possessed DSAs against HLA-A, B, and/or DP, compared with only 1 (1%) of 78 controls. Therefore, the presence of DSAs was significantly associated with graft failure (odds ratio = 22.84; 95% confidence interval, 3.57-infinity; P < .001). These results indicate that the presence of pretransplantation DSAs in recipients of unrelated donor HCT is associated with failed engraftment and should be considered in HCT donor selection.
authors.affiliation: National Marrow Donor Program, Minneapolis, MN 55413, USA. sspellma@nmdp.org
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.forename: Robert
authors.initials: R
authors.lastname: Bray
authors.forename: Sandra
authors.initials: S
authors.lastname: Rosen-Bronson
authors.forename: Michael
authors.initials: M
authors.lastname: Haagenson
authors.forename: John
authors.initials: J
authors.lastname: Klein
authors.forename: Susan
authors.initials: S
authors.lastname: Flesch
authors.forename: Cynthia
authors.initials: C
authors.lastname: Vierra-Green
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006086:Graft vs Host Disease / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D007938:Leukemia / Q000276:immunology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000601:surgery; D011300:Preoperative Care; D011379:Prognosis; D012189:Retrospective Studies; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies