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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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Submitted April 16, 2004
Accepted October 29, 2004
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 Ottinger, Stanislav Ferencik, Ahmet H Elmaagacli, Rudolf Peceny, Rudolf Trenschel, and Hans Grosse-Wilde
Department of Bone Marrow Transplantation, University Hospital of Essen, Essen, Germany
Department of Bone Marrow Transplantation, University Hospital of Essen, Essen, Germany; Institute of Immunology, University Hospital of Essen, Essen, Germany
Institute of Immunology, University Hospital of Essen, Essen, Germany
* Corresponding author; email: dietrich.beelen{at}uni-essen.de.
It remains presently 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 HLA-identical (N=237: 22%), HLA class I disparate (N=89: 18%), and KIR ligand incompatible transplants (N=48: 5%) (p<0.04). 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 transplants (RR 0.24) (p<0.008). 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 transplants, respectively (p<0.02). Unlike some other reports, no beneficial effect of KIR ligand incompatibility on other major endpoints of allogeneic HSCT (transplant-related mortality, 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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