title: The favorable role of homozygosity for killer immunoglobulin-like receptor (KIR) A haplotype in patients with advanced-stage classic Hodgkin lymphoma.
abstract: BACKGROUND
  Interim positron emission tomography after 2 cycles of ABVD (iPET-2) is a good predictor of outcome in advanced-stage classic Hodgkin lymphoma. So far, there are no other prognostic biomarkers capable of identifying chemotherapy refractory patients with comparable accuracy. Despite the considerable amount of evidence suggesting that antitumor immune surveillance is downregulated in classic Hodgkin lymphoma (cHL), few data exist on the impairment of natural killer cell function and the role of their killer immunoglobulin-like receptors (KIRs).
  
  
  METHODS
  We investigated KIR gene frequencies, KIR haplotypes, and KIR-ligand combinations in a cohort of 135 patients with advanced-stage classic Hodgkin lymphoma and 221 healthy controls. We furthermore evaluated the correlation of KIR genes and KIR haplotypes with the achievement of negative iPET-2.
  
  
  RESULTS
  In the cohort of patients, the 5-year overall survival and progression-free survival were 93.6 and 79%, respectively. Homozygosity for KIR A haplotype and the HLA-C1 KIR ligand (KIR-AA/C1C1) was significantly higher in healthy controls (15.7 vs. 4.8%, p = 0.001). The KIR-AA genotype resulted to have a significant predictive power for achieving iPET-2 negativity (p = 0.039).
  
  
  CONCLUSIONS
  Homozygosity for KIR A haplotype offers protection against classic Hodgkin lymphoma. The association found for the KIR-AA genotype and achievement of negative iPET-2 suggests that KIR-AA could be used in clinical practice to enhance the chemosensitivity predictive power of iPET-2. Our results point to the possibility of adapting treatment strategies based on the combination of KIR biomarkers and PET scan.
authors.affiliation: Hematology Unit, Department of Medical Sciences "M. Aresu", University of Cagliari, Via Is Guadazzonis, 3, 09126, Cagliari, Italy. lanasa@tiscali.it.|Bone Marrow Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy. lanasa@tiscali.it.
authors.forename: Giorgio
authors.initials: G
authors.lastname: La Nasa
authors.affiliation: Bone Marrow Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Greco
authors.affiliation: Regional Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Littera
authors.affiliation: Bone Marrow Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Oppi
authors.affiliation: Hematology Department and BMT Unit, Azienda Ospedaliera S. Croce e Carle, Cuneo, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Celeghini
authors.affiliation: Bone Marrow Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Caria
authors.affiliation: Regional Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Lai
authors.affiliation: Regional Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Porcella
authors.affiliation: Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera BMM, Reggio Calabria, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Martino
authors.affiliation: Division of Hematology, Azienda Policlinico-OVE, University of Catania, Catania, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Romano
authors.affiliation: Division of Hematology, Azienda Policlinico-OVE, University of Catania, Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.affiliation: Research, Innovation and Statistics Department, Centre Antoine Lacassagne, Nice Cedex 2, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gallamini
authors.affiliation: Medical Genetics, Department of Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Carcassi
authors.affiliation: Hematology Unit, Department of Medical Sciences "M. Aresu", University of Cagliari, Via Is Guadazzonis, 3, 09126, Cagliari, Italy.|Bone Marrow Transplant Center, R. Binaghi Hospital, ASL 8, Cagliari, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Caocci
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D001761:Bleomycin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D019788:Fluorodeoxyglucose F18; D005787:Gene Frequency; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006689:Hodgkin Disease / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017063:Outcome Assessment, Health Care; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D054340:Receptors, KIR / Q000235:genetics*; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; D006680:HLA Antigens; D054340:Receptors, KIR; D019788:Fluorodeoxyglucose F18; D001761:Bleomycin; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin
keywords: Hodgkin lymphoma; KIR A haplotype; Killer immunoglobulin-like receptors; Natural killer cells; Positron emission tomography