title: Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors.
abstract: Killer immunoglobulin-like receptor (KIR) ligand incompatibility in the graft-versus-host direction was demonstrated to be associated with improved outcome in patients given haploidentical, T-cell-depleted hematopoietic stem cell transplants (HSCTs). The goal of this study was to evaluate whether that observation could be generalized for patients receiving unmanipulated HSCTs from unrelated donors (URD). One hundred thirty patients with hematologic malignancies entered the study. Graft-versus-host disease (GVHD) prophylaxis was uniform and consisted of cyclosporin, short-term methotrexate, and pretransplantation antithymocyte globulin (ATG). Patients were divided into those with (n = 20) and those without (n = 110) KIR ligand incompatibility with respect to their donors. At 4.5 years patients with KIR ligand incompatibility had higher probability of overall survival (87% versus 48%, P =.006) and disease-free survival (87% versus 39%, P =.0007) compared with those without KIR ligand incompatibility. Transplant-related mortality for the 2 groups equaled 6% and 40% (P =.01), respectively. Relapse rates for patients receiving transplants from a donor with or without KIR ligand incompatibility were 6% and 21%, respectively (P =.07). All patients with myeloid malignancies receiving transplants from KIR ligand-disparate donors (n = 13) are alive and disease free. These data indicate that natural killer (NK) cell alloreactivity is associated with better outcome after URD-HSC transplantation when ATG is used as part of GVHD prophylaxis.
authors.affiliation: Department of Haematology and Bone Marrow Transplantation, Silesian Medical Academy, Katowice, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Giebel
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Teresa
authors.initials: T
authors.lastname: Lamparelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Velardi
authors.forename: Stella
authors.initials: S
authors.lastname: Davies
authors.forename: Guido
authors.initials: G
authors.lastname: Frumento
authors.forename: Rita
authors.initials: R
authors.lastname: Maccario
authors.forename: Federico
authors.initials: F
authors.lastname: Bonetti
authors.forename: Jerzy
authors.initials: J
authors.lastname: Wojnar
authors.forename: Miryam
authors.initials: M
authors.lastname: Martinetti
authors.forename: Francesco
authors.initials: F
authors.lastname: Frassoni
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giorgiani
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacigalupo
authors.forename: Jerzy
authors.initials: J
authors.lastname: Holowiecki
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008297:Male; D011446:Prospective Studies; D011971:Receptors, Immunologic / Q000276:immunology*; D054340:Receptors, KIR; D012008:Recurrence; D016019:Survival Analysis; D014019:Tissue Donors; D014181:Transplantation Immunology; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR