title: Chronic natural killer lymphoproliferative disorders: characteristics of an international cohort of 70 patients.
abstract: BACKGROUND
  The 2008 World Health Organization (WHO) classification distinguishes three entities among the large granular lymphocytic leukemia (LGL leukemia): T-cell LGL leukemia (T-LGL leukemia), aggressive natural killer (NK) cell leukemia, and chronic NK lymphoproliferative disorders (LPD), the later considered as a provisional entity. Only a few and small cohorts of chronic NK LPD have been published.
  
  
  METHODS
  We report here clinicobiological features collected retrospectively from 70 cases of chronic NK LPD, and compared with those of T-LGL leukemia.
  
  
  RESULTS
  There were no statistical differences between chronic NK LPD and T-LGL leukemia concerning median age [61 years (range 23-82 years)], organomegaly (26%), associated autoimmune diseases (24%), and associated hematological malignancies (11%). Patients with chronic NK LPD were significantly less symptomatic (49% versus 18%, P < 0.001) and the association with rheumatoid arthritis was more rarely observed (7% versus 17%, P = 0.03). The neutropenia (<0.5 × 10(9)/l) was less severe in chronic NK LPD (33% versus 61%, P < 0.001) without difference in the rate of recurrent infections. STAT3 mutation was detected in 12% of the cohort, which is lower than the frequency observed in T-LGL leukemia. Thirty-seven percent of the patients required specific therapy. Good results were obtained with cyclophosphamide. Overall and complete response rates were, respectively, 69% and 56%. Overall survival was 94% at 5 years.
  
  
  CONCLUSIONS
  This study suggests very high similarities between chronic NK LPD and T-LGL leukemias. Since chronic NK LPD is still a provisional entity, our findings should be helpful when considering further revisions of the WHO classification.
authors.affiliation: Department of Clinical Hematology, Rennes University Hospital, Rennes, France; Department of Pathology, Rennes University Hospital, Rennes, France.
authors.forename: E
authors.initials: E
authors.lastname: Poullot
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Zambello
authors.affiliation: University of Virginia Cancer Center, University of Virginia School of Medicine, Charlottesville, USA.
authors.forename: F
authors.initials: F
authors.lastname: Leblanc
authors.affiliation: Department of Clinical Hematology, Clinique Cesson-Sévigné, Cesson-Sévigné.
authors.forename: B
authors.initials: B
authors.lastname: Bareau
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy.
authors.forename: E
authors.initials: E
authors.lastname: De March
authors.affiliation: Department of Hematology-Immunology and Cell Therapy, Rennes University Hospital, Rennes; INSERM UMR 917 Faculté de médecine Université Rennes 1, Rennes.
authors.forename: M
authors.initials: M
authors.lastname: Roussel
authors.affiliation: Department of Hematology-Immunology and Cell Therapy, Rennes University Hospital, Rennes.
authors.forename: M L
authors.initials: ML
authors.lastname: Boulland
authors.affiliation: Department of Clinical Hematology, Rennes University Hospital, Rennes, France; INSERM UMR 917 Faculté de médecine Université Rennes 1, Rennes.
authors.forename: R
authors.initials: R
authors.lastname: Houot
authors.affiliation: Department of Clinical Investigation, Rennes University Hospital, Rennes, France.
authors.forename: A
authors.initials: A
authors.lastname: Renault
authors.affiliation: Department of Clinical Hematology, Clinique Cesson-Sévigné, Cesson-Sévigné; INSERM UMR 917 Faculté de médecine Université Rennes 1, Rennes.
authors.forename: T
authors.initials: T
authors.lastname: Fest
authors.affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Semenzato
authors.affiliation: University of Virginia Cancer Center, University of Virginia School of Medicine, Charlottesville, USA.
authors.forename: T
authors.initials: T
authors.lastname: Loughran
authors.affiliation: Department of Clinical Hematology, Rennes University Hospital, Rennes, France; INSERM UMR 917 Faculté de médecine Université Rennes 1, Rennes; Department of Clinical Investigation, Rennes University Hospital, Rennes, France. Electronic address: thierry.lamy@univ-rennes1.fr.
authors.forename: T
authors.initials: T
authors.lastname: Lamy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000473:pathology*; D054066:Leukemia, Large Granular Lymphocytic / Q000145:classification / Q000235:genetics / Q000473:pathology*; D008232:Lymphoproliferative Disorders / Q000145:classification / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000235:genetics; D014944:World Health Organization
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: large granular lymphocytic/pathology; leukemia; natural killer cells
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