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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.
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 leukemiasFrom 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 immunoglobulinlike 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 Idisparate (n = 89; 18%), and KIR ligandincompatible 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 Idisparate, KIR ligandincompatible transplantations (RR 0.24) (P < .008). The primary graft failure rates, however, increased from 0.4% after HLA class Iidentical to 2.3% after HLA class Idisparate, and to 6.3% after KIR ligandincompatible 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 ligandincompatible donors provides a superior long-term antileukemic efficacy in patients with myeloid malignancies.
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