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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2594-2600.
Prepublished online as a Blood First Edition Paper on November 9, 2004; DOI 10.1182/blood-2004-04-1441.


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TRANSPLANTATION

Genotypic inhibitory killer immunoglobulin-like receptor ligand incompatibility enhances the long-term antileukemic effect of unmodified allogeneic hematopoietic stem cell transplantation in patients with myeloid leukemias

Dietrich W. Beelen, Hellmut D. Ottinger, Stanislav Ferencik, Ahmet H. Elmaagacli, Rudolf Peceny, Rudolf Trenschel, and Hans Grosse-Wilde

From the Department of Bone Marrow Transplantation and Institute of Immunology, University Hospital of Essen, Germany.

It remains controversial whether alloreactive donor-derived natural killer (NK) cells display graft-versus-leukemia reactions after unmodified allogeneic hematopoietic stem cell transplantation (HSCT). The present study evaluated the role of inhibitory killer immunoglobulin–like receptor (KIR) ligand incompatibility using a well-defined and uniform setting of unmodified allogeneic HSCT in 374 patients with myeloid leukemias. The most striking finding was a significant heterogeneity in the 5-year estimates of hematologic leukemic relapse after human leukocyte antigen (HLA)–identical (n = 237; 22%), HLA class I–disparate (n = 89; 18%), and KIR ligand–incompatible transplantations (n = 48; 5%) (P < .04). Multivariate analysis confirmed that the relative relapse risk (RR) was influenced by HLA class I disparity alone (RR 0.49), but was lowest after HLA class I–disparate, KIR ligand–incompatible transplantations (RR 0.24) (P < .008). The primary graft failure rates, however, increased from 0.4% after HLA class I–identical to 2.3% after HLA class I–disparate, and to 6.3% after KIR ligand–incompatible transplantations, respectively (P < .02). Unlike some other reports, no beneficial effect of KIR ligand incompatibility on other major endpoints of allogeneic HSCT (transplantation-related mortality, and overall and event-free survival) was detectable in the present study. In conclusion, unmodified allogeneic HSCT from KIR ligand–incompatible donors provides a superior long-term antileukemic efficacy in patients with myeloid malignancies.


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