Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT.
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.
Miller
Jeffery S
JS
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
Cooley
Sarah
S
Parham
Peter
P
Farag
Sherif S
SS
Verneris
Michael R
MR
McQueen
Karina L
KL
Guethlein
Lisbeth A
LA
Trachtenberg
Elizabeth A
EA
Haagenson
Michael
M
Horowitz
Mary M
MM
Klein
John P
JP
Weisdorf
Daniel J
DJ
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
D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR