title: Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT.
abstract: Natural killer (NK) cells can alter the outcome of hematopoietic cell transplantation (HCT) if donor alloreactivity targets the recipient. Since most NK cells express inhibitory killer-immunoglobulin receptors (KIRs), we hypothesized that the susceptibility of recipient cells to donor NK cell-mediated lysis is genetically predetermined by the absence of known KIR ligands. We analyzed data from 2062 patients undergoing unrelated donor HCT for acute myeloid leukemia (AML; n = 556), chronic myeloid leukemia (CML; n = 1224), and myelodysplastic syndrome (MDS; n = 282). Missing 1 or more KIR ligands versus the presence of all ligands protected against relapse in patients with early myeloid leukemia (relative risk [RR] = 0.54; n = 536, 95% confidence interval [CI] 0.30-0.95, P = .03). In the subset of CML patients that received a transplant beyond 1 year from diagnosis (n = 479), missing a KIR ligand independently predicted a greater risk of developing grade 3-4 acute graft-versus-host disease (GVHD; RR = 1.58, 95% CI 1.13-2.22; P = .008). These data support a genetically determined role for NK cells following unrelated HCT in myeloid leukemia.
authors.affiliation: Divisions of Adult and Pediatric Hematology, Oncology and Transplantation, University of Minnesota Cancer Center, Harvard Street at East River Road, Minneapolis, MN 55455, USA. mille011@umn.edu
authors.forename: Jeffery S
authors.initials: JS
authors.lastname: Miller
authors.forename: Sarah
authors.initials: S
authors.lastname: Cooley
authors.forename: Peter
authors.initials: P
authors.lastname: Parham
authors.forename: Sherif S
authors.initials: SS
authors.lastname: Farag
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
authors.forename: Karina L
authors.initials: KL
authors.lastname: McQueen
authors.forename: Lisbeth A
authors.initials: LA
authors.lastname: Guethlein
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Trachtenberg
authors.forename: Michael
authors.initials: M
authors.lastname: Haagenson
authors.forename: Mary M
authors.initials: MM
authors.lastname: Horowitz
authors.forename: John P
authors.initials: JP
authors.lastname: Klein
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
mesh_terms: D020022:Genetic Predisposition to Disease; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000276:immunology; D008024:Ligands; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000276:immunology; D011971:Receptors, Immunologic / Q000737:chemistry / Q000276:immunology*; D054340:Receptors, KIR; D012008:Recurrence; D012042:Registries; D012306:Risk; D014184:Transplantation, Homologous / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR