KIR Ligands and Prediction of Relapse after Unrelated Donor Hematopoietic Cell Transplantation for Hematologic Malignancy

K.C. Hsu, T. Gooley, M. Malkki, C. Pinto-Agnello, B. Dupont, J-D. Bignon, M. Bornhauser, Frank Christiansen, A. Gratwohl, Y. Morishima, M. Oudshoorn, O. Ringden, J.J. Van Rood, E. Petersdorf

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Abstract

Recurrent malignancy remains a significant complication after allogeneic hematopoietic cell transplantation (HCT). Efforts to decrease relapse have included donor lymphocyte infusion to stimulate donor anti-recipient T-cell allorecognition of major and minor histocompatibility differences. Recently, alloreactive effects of donor natural killer cell-mediated inhibitory killer immunoglobulin-like receptor (KIR) recognition of recipient HLA-C and -B ligands have been described. We examined KIR ligand effects on risk of relapse in 1770 patients undergoing myeloablative T-replete HCT from HLA-matched or -mismatched unrelated donors for the treatment of myeloid and lymphoid leukemias. KIR ligands defined by HLA-B and -C genotypes were used to determine donor-recipient ligand incompatibility or recipient lack of KIR ligand. Among HLA-mismatched transplantations, recipient homozygosity for HLA-B or -C KIR epitopes predicted lack of KIR ligand and was associated with a decreased hazard of relapse (hazard ratio, 0.61; 95% confidence interval,.043-0.85; P =.004). Absence of HLA-C group 2 or HLA-Bw4 KIR ligands was associated with lower hazards of relapse (hazard ratio, 0.47; 95% confidence interval, 0.28-0.79, P =.004; hazard ratio, 0.56; 95% confidence interval, 0.33-0.97; P =.04, respectively). The decrease in hazard of relapse in patients with acute myelogenous leukemia was similar to that in patients with chronic myelogenous leukemia and acute lymphoblastic leukemia (P =.95). Recipient homozygosity for HLA-B or -C epitopes that define KIR ligands is likely to be a predictive factor for leukemia relapse after myeloablative HCT from HLA-mismatched unrelated donors. This effect was not observed in HLA-identical unrelated transplants. (C) 2006 American Society for Blood and Marrow Transplantation.
Original languageEnglish
Pages (from-to)828-836
JournalBiology of Blood and Marrow Transplantation
Volume12
DOIs
Publication statusPublished - 2006

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