title: Inhibitory killer cell immunoglobulin-like receptor (iKIR) mismatches improve survival after T-cell-repleted haploidentical transplantation.
abstract: Alloreactivity triggered by interaction between killer cell immunoglobulin-like receptors (KIRs) and natural killer (NK) cells plays a role in the graft-versus-tumor effect after hematopoietic stem cell transplantation (SCT). Our aim in this study was to evaluate this role in the setting of T-cell-repleted haploidentical SCT with postinfusion high-dose cyclophosphamide (PT-Cy). We included 33 patients. Among patient-donor pairs with at least 1 inhibitory KIR (iKIR) gene mismatch, event-free survival (EFS) and cumulative incidence of relapse 1 year after transplant were significantly better (85% vs. 37% [P = 0.008] and 18% vs. 46% [P = 0.041], respectively). A subanalysis in 12 patients with Hodgkin's lymphoma (HL) showed an improvement in EFS 1 year after transplant in those patients with KIR ligand mismatch (100% vs. 25%, P = 0.012), although overall survival (OS) was not affected (85% vs. 80%, P = 0.2). Eight of 12 patient-donors pairs presented iKIR mismatches. Of note, this outcome was better in the small subgroup, both for EFS (100% vs. 25%, P = 0.012) and for OS (100% vs. 37%, P = 0.004). Our data suggest that in the setting of T-cell-repleted haploidentical SCT with PT-Cy, iKIR mismatch is associated with improved survival, with particularly good results for both iKIR and KIR ligand mismatches in patients with HL.
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Mariana
authors.initials: M
authors.lastname: Bastos-Oreiro
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Anguita
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Martínez-Laperche
authors.affiliation: Programa de investigación clínica, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Fernández
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Buces
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Almudena
authors.initials: A
authors.lastname: Navarro
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Pascual
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Pérez-Corral
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Pascual
authors.initials: P
authors.lastname: Balsalobre
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Muñoz
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Mi
authors.initials: M
authors.lastname: Kwon
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Serrano
authors.affiliation: Servicio de Hemato-Oncología Pediatrica, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Perez-Martinez
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Ismael
authors.initials: I
authors.lastname: Buño
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Gayoso
authors.affiliation: Servicio de Hematología y Hemoterapia, Hospital General Universitario Gregorio Marañón, Madrid, Spain.|Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: José Luís
authors.initials: JL
authors.lastname: Díez-Martín
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D008024:Ligands; D054340:Receptors, KIR
keywords: GvL; KIR; NK cells; T-cell repleted haploidentical transplantation