title: Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes.
abstract: Inhibitory killer immunoglobulin (Ig)-like receptors (KIRs) recognize HLA-C and -B epitopes on target cells, thereby regulating natural killer (NK) cell activity. In 178 patients receiving T-cell-depleted HLA-identical sibling transplants for acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS), analysis of donor KIR genotype with HLA genotype demonstrated that 62.9% of the patients lacked an HLA ligand for donor-inhibitory KIR. Lack of HLA ligand for donor-inhibitory KIR (missing KIR ligand) had no effect on disease-free survival (DFS), overall survival (OS), or relapse in patients receiving transplants for CML and ALL. In patients with AML and MDS, however, there was a significant missing KIR ligand effect on DFS (P = .014; hazard ratio [HR], 0.53; 95% confidence interval [95% CI], 0.28-0.88) and OS (P = .03; HR, 0.53; 95% CI, 0.3-0.93). Incidence of relapse was also lower in patients with AML and MDS who lacked the HLA ligand for donor-inhibitory KIR (P = .04; HR, 0.41; 95% CI, 0.18-0.97). AML and MDS patients lacking 2 HLA ligands for donor-inhibitory KIR had the highest DFS (P = .002) and OS (P = .003). There was no significant contribution of donor-activating KIR to transplantation outcome in these patients. These data indicate that the absence of class I ligand in the recipient for donor-inhibitory KIR can be a prognostic factor for transplantation outcome in HLA-identical sibling transplantation and that the lack of HLA-C or -B ligands for donor-inhibitory KIR can contribute to improved outcomes for patients with AML and MDS.
authors.affiliation: Allogeneic Marrow Transplantation Service and the Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York 10021, USA. hsuk@mskcc.org <hsuk@mskcc.org>
authors.forename: Katharine C
authors.initials: KC
authors.lastname: Hsu
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Keever-Taylor
authors.forename: Andrew
authors.initials: A
authors.lastname: Wilton
authors.forename: Clara
authors.initials: C
authors.lastname: Pinto
authors.forename: Glenn
authors.initials: G
authors.lastname: Heller
authors.forename: Knarik
authors.initials: K
authors.lastname: Arkun
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
authors.forename: Mary M
authors.initials: MM
authors.lastname: Horowitz
authors.forename: Bo
authors.initials: B
authors.lastname: Dupont
mesh_terms: D000465:Algorithms; D000483:Alleles; D001854:Bone Marrow Cells / Q000276:immunology; D018572:Disease-Free Survival; D000939:Epitopes; D005192:Family Health; D005260:Female; D005838:Genotype; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D015236:HLA-C Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000628:therapy*; D008024:Ligands; D008297:Male; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000628:therapy; D015345:Oligonucleotide Probes / Q000737:chemistry; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000628:therapy; D016016:Proportional Hazards Models; D011971:Receptors, Immunologic / Q000235:genetics* / Q000276:immunology*; D054340:Receptors, KIR; D012008:Recurrence; D012189:Retrospective Studies; D012306:Risk; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000939:Epitopes; D006680:HLA Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D008024:Ligands; D015345:Oligonucleotide Probes; D011971:Receptors, Immunologic; D054340:Receptors, KIR
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