Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT

Jeffery S. Miller, Sarah Cooley, Peter Parham, Sherif S. Farag, Michael R. Verneris, Karina L. McQueen, Lisbeth A. Guethlein, Elizabeth A. Trachtenberg, Michael Haagenson, Mary M. Horowitz, John P. Klein, Daniel J. Weisdorf

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215 Scopus citations

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 pre-determined 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.

Original languageEnglish (US)
Pages (from-to)5058-5061
Number of pages4
JournalBlood
Volume109
Issue number11
DOIs
StatePublished - Jun 1 2007

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Miller, J. S., Cooley, S., Parham, P., Farag, S. S., Verneris, M. R., McQueen, K. L., Guethlein, L. A., Trachtenberg, E. A., Haagenson, M., Horowitz, M. M., Klein, J. P., & Weisdorf, D. J. (2007). Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT. Blood, 109(11), 5058-5061. https://doi.org/10.1182/blood-2007-01-065383