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Blood, 1 June 2007, Vol. 109, No. 11, pp. 5058-5061.
Prepublished online as a Blood First Edition Paper on February 22, 2007; DOI 10.1182/blood-2007-01-065383.
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TRANSPLANTATION
Brief Report
Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT
Jeffery S. Miller1,
Sarah Cooley1,
Peter Parham2,
Sherif S. Farag3,
Michael R. Verneris1,
Karina L. McQueen2,
Lisbeth A. Guethlein2,
Elizabeth A. Trachtenberg4,
Michael Haagenson5,
Mary M. Horowitz6,
John P. Klein7, and
Daniel J. Weisdorf1
1 Divisions of Adult and Pediatric Hematology, Oncology and Transplantation, University of Minnesota Cancer Center, Minneapolis;
2 Department of Structural Biology, Stanford University School of Medicine, CA;
3 Division of Hematology and Oncology, Indiana University School of Medicine, Indianapolis;
4 Center for Genetics, Children's Hospital & Research Center Oakland, CA;
5 Center for International Blood and Marrow Transplant Research, National Marrow Donor Program, Minneapolis, MN;
6 Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee;
7 Division of Biostatistics, Medical College of Wisconsin, Milwaukee
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.

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