title: Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229 cases.
abstract: BACKGROUND
  Large granular lymphocyte leukemia is a rare lymphoproliferative disorder associated with autoimmune diseases and impaired hematopoiesis. This study describes the clinical and biological characteristics of 229 patients with T-cell or NK-cell large granular lymphocyte leukemia.
  
  
  METHODS
  The diagnosis was based on a large granular lymphocyte expansion (> 0.5x10(9)/L) lasting more than 6 months. Monoclonal T-cell receptor gamma gene rearrangement was detected in all the cases of T-cell large granular lymphocyte leukemia. Patients with chronic NK-cell lymphocytosis had an indolent disease, while those with multiorgan large granular lymphocyte infiltration and an aggressive clinical disease were considered to have NK-cell large granular lymphocyte leukemia.
  
  
  RESULTS
  The diagnosis of T-cell large granular lymphocyte leukemia was confirmed in 201 cases, chronic NK-cell lymphocytosis in 27 cases and NK-cell large granular lymphocyte leukemia in one case. Associated autoimmune diseases or other neoplasms were present in 74 and 32 cases, respectively. One hundred patients (44%) required treatment, mainly for neutropenia-associated infections (n=45), symptomatic autoimmune diseases (n =24), transfusion-dependant anemia (n=18), and other causes (n=13). Patients were treated with steroids (n= 33), methotrexate (n=62), cytoxan (n=32), or cyclosporine (n=24) either as first-, second-, third- or fourth-line therapy. The overall response rate at 3 months and complete response rate for the various treatments were as follows: steroids (12% and 3%), methotrexate (55% and 21%), cytoxan (66% and 47%), cyclosporine (21% and 4%), respectively. Four out of 13 patients responded to splenectomy. Eleven out of 15 patients responded to cytoxan after methotrexate treatment had failed. The mean number of treatments was 3.4 (range, 1-7). There were 15 large granular lymphocyte leukemia-related deaths.
  
  
  CONCLUSIONS
  Patients with T-cell large granular lymphocyte leukemia and chronic NK-cell lymphocytosis have similar clinical and biological features and responses to treatment. First-line therapy with cytoxan should be tested in a prospective trial.
authors.affiliation: Service d'Hématologie Clinique, Hôpital Pontchaillou, CHU de Rennes 35033, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Bareau
authors.forename: Jérôme
authors.initials: J
authors.lastname: Rey
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamidou
authors.forename: Jean
authors.initials: J
authors.lastname: Donadieu
authors.forename: Jeff
authors.initials: J
authors.lastname: Morcet
authors.forename: Oumedaly
authors.initials: O
authors.lastname: Reman
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schleinitz
authors.forename: Olivier
authors.initials: O
authors.lastname: Tournilhac
authors.forename: Mikael
authors.initials: M
authors.lastname: Roussel
authors.forename: Thierry
authors.initials: T
authors.lastname: Fest
authors.forename: Thierry
authors.initials: T
authors.lastname: Lamy
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D007694:Killer Cells, Natural / Q000473:pathology*; D054066:Leukemia, Large Granular Lymphocytic / Q000175:diagnosis* / Q000453:epidemiology* / Q000628:therapy; D008218:Lymphocytosis / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D012042:Registries; D013601:T-Lymphocytes / Q000473:pathology*; D016896:Treatment Outcome