title: Donor activating KIR3DS1 is associated with decreased acute GVHD in unrelated allogeneic hematopoietic stem cell transplantation.
abstract: The natural killer cell receptor KIR3DS1 is associated with improved outcome in malignancies, infections, and autoimmune diseases, but data for the impact of KIR3DS1 in HSCT are inconsistent. Using genomic DNA from the National Marrow Donor Program, we performed donor KIR genotyping for 1087 patients who received an unrelated hematopoietic stem cell transplantation. A total of 33% of donors were KIR3DS1(+). Compared with KIR3DS1(-) donors, donor KIR3DS1 was associated with lower-grade II-IV acute graft-versus-host disease (GVHD; odds ratio = 0.71; 95% confidence interval, 0.55-0.92; P = .009), but not with relapse (hazard ratio = 0.97; 95% confidence interval, 0.73-1.29; P = .82). Furthermore, grade II-IV acute GVHD, overall mortality, and transplantation-related mortality all decreased as the number of copies of donor KIR3DS1 increased (P = .007, P = .03, and P = .02, respectively), with the lowest failure rate occurring among patients homozygous for donor KIR3DS1. Selection of donors with KIR3DS1 may decrease acute GVHD without compromising relapse-free survival, separating the graft-versus-tumor effect from unwanted GVHD.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Venstrom
authors.forename: Ted A
authors.initials: TA
authors.lastname: Gooley
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.forename: James
authors.initials: J
authors.lastname: Pring
authors.forename: Mari
authors.initials: M
authors.lastname: Malkki
authors.forename: Bo
authors.initials: B
authors.lastname: Dupont
authors.forename: Effie
authors.initials: E
authors.lastname: Petersdorf
authors.forename: Katharine C
authors.initials: KC
authors.lastname: Hsu
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D054349:Receptors, KIR3DS1 / Q000235:genetics*; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D054349:Receptors, KIR3DS1