title: 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.
abstract: 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.
authors.affiliation: Department of Bone Marrow Transplantation, Institute of Immunology, University Hospital of Essen, Hufelandstrasse 55, 45122 Essen, Germany. dietrich.beelen@uni-essen.de
authors.forename: Dietrich W
authors.initials: DW
authors.lastname: Beelen
authors.forename: Hellmut D
authors.initials: HD
authors.lastname: Ottinger
authors.forename: Stanislav
authors.initials: S
authors.lastname: Ferencik
authors.forename: Ahmet H
authors.initials: AH
authors.lastname: Elmaagacli
authors.forename: Rudolf
authors.initials: R
authors.lastname: Peceny
authors.forename: Rudolf
authors.initials: R
authors.lastname: Trenschel
authors.forename: Hans
authors.initials: H
authors.lastname: Grosse-Wilde
mesh_terms: D000293:Adolescent; D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006648:Histocompatibility / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D007951:Leukemia, Myeloid / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008024:Ligands; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000276:immunology*; D054340:Receptors, KIR; D012008:Recurrence; D012189:Retrospective Studies; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR