title: Haploidentical hematopoietic transplantation from KIR ligand-mismatched donors with activating KIRs reduces nonrelapse mortality.
abstract: Because activating killer cell immunoglobulinlike receptors (KIRs) are heterogeneously expressed in the population, we investigated the role of donor activating KIRs in haploidentical hematopoietic transplants for acute leukemia. Transplants were grouped according to presence vs absence of KIR-ligand mismatches in the graft-vs-host direction (ie, of donor-vs-recipient natural killer [NK]-cell alloreactivity). In the absence of donor-vs-recipient NK-cell alloreactivity, donor activating KIRs had no effects on outcomes. In the 69 transplant pairs with donor-vs-recipient NK-cell alloreactivity, transplantation from donors with KIR2DS1 and/or KIR3DS1 was associated with reduced risk of nonrelapse mortality, largely infection related (KIR2DS1 present vs absent: hazard ratio [HR], 0.25; P = .01; KIR3DS1 present vs absent: HR, 0.18; P = .006), and better event-free survival (KIR2DS1 present vs absent: HR, 0.31; P = .011; KIR3DS1 present vs absent: HR, 0.30; P = .008). Transplantation from donors with KIR2DS1 and/or KIR3DS1 was also associated with a 50% reduction in infection rate (P = .003). In vitro analyses showed that KIR2DS1 binding to its HLA-C2 ligand upregulated inflammatory cytokine production by alloreactive NK cells in response to infectious challenges. Because ∼40% of donors able to exert donor-vs-recipient NK-cell alloreactivity carry KIR2DS1 and/or KIR3DS1, searching for them may become a feasible, additional criterion in donor selection.
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine and.
authors.forename: Antonella
authors.initials: A
authors.lastname: Mancusi
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine and.
authors.forename: Loredana
authors.initials: L
authors.lastname: Ruggeri
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine and.
authors.forename: Elena
authors.initials: E
authors.lastname: Urbani
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine and.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pierini
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine and.
authors.forename: Maria Speranza
authors.initials: MS
authors.lastname: Massei
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine and.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carotti
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine and.
authors.forename: Adelmo
authors.initials: A
authors.lastname: Terenzi
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine and.
authors.forename: Franca
authors.initials: F
authors.lastname: Falzetti
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine and.
authors.forename: Antonella
authors.initials: A
authors.lastname: Tosti
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine and.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Topini
authors.affiliation: Division of Microbiology, Department of Experimental Medicine, University of Perugia, Perugia, Italy;
authors.forename: Silvia
authors.initials: S
authors.lastname: Bozza
authors.affiliation: Division of Microbiology, Department of Experimental Medicine, University of Perugia, Perugia, Italy;
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
authors.affiliation: Blood Bank, Ospedale Santa Maria della Misericordia, Perugia, Italy;
authors.forename: Rita
authors.initials: R
authors.lastname: Tognellini
authors.affiliation: Immunotherapy Laboratory, Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland; and.
authors.forename: Martin
authors.initials: M
authors.lastname: Stern
authors.affiliation: Division of Hematology and Bone Marrow Transplant Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Aversa
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine and.
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Martelli
authors.affiliation: Division of Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine and.
authors.forename: Andrea
authors.initials: A
authors.lastname: Velardi
mesh_terms: D056426:Genetic Loci; D005838:Genotype; D006086:Graft vs Host Disease / Q000209:etiology; D015236:HLA-C Antigens / Q000276:immunology / Q000378:metabolism; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D007938:Leukemia / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D011485:Protein Binding; D054340:Receptors, KIR / Q000235:genetics* / Q000378:metabolism*; D012189:Retrospective Studies; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D015236:HLA-C Antigens; C048767:HLA-C*02 antigen; C496212:KIR2DS1 protein, human; D054340:Receptors, KIR