title: Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia.
abstract: BACKGROUND
  To determine whether chlorambucil treatment benefits patients with indolent chronic lymphocytic leukemia (CLL), we conducted two randomized trials in 1535 patients with previously untreated stage A CLL.
  
  
  METHODS
  In the first trial, 609 patients were randomly assigned to receive either daily chlorambucil or no treatment; in the second trial, 926 patients were randomly assigned to receive either intermittent chlorambucil plus prednisone or no treatment. Median follow-up for the first and second trials exceeded 11 and 6 years, respectively. The end points were overall survival, response to treatment, and disease progression.
  
  
  RESULTS
  Treatment of indolent CLL did not increase survival in either trial. In the treated group, as compared with the untreated group, the relative risk of death was 1.14 (95 percent confidence interval, 0.92 to 1.41; P=0.23) in the first trial and 0.96 (95 percent confidence interval, 0.75 to 1.23; P=0.74) in the second trial, with 76 percent and 69 percent of patients, respectively, having a response to therapy. Although chlorambucil slowed disease progression, there was no effect on overall survival. In the untreated group in the first trial, 49 percent of patients did not have progression to more advanced disease and did not need therapy after follow-up of more than 11 years; however, 27 percent of patients with stage A CLL died of causes related to the disease.
  
  
  CONCLUSIONS
  Chlorambucil does not prolong survival in patients with stage A CLL. Since deferring therapy until the disease progresses to stage B or C does not compromise survival, treatment of indolent CLL is unnecessary.
authors.affiliation: Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Dighiero
authors.forename: K
authors.initials: K
authors.lastname: Maloum
authors.forename: B
authors.initials: B
authors.lastname: Desablens
authors.forename: B
authors.initials: B
authors.lastname: Cazin
authors.forename: M
authors.initials: M
authors.lastname: Navarro
authors.forename: R
authors.initials: R
authors.lastname: Leblay
authors.forename: M
authors.initials: M
authors.lastname: Leporrier
authors.forename: J
authors.initials: J
authors.lastname: Jaubert
authors.forename: G
authors.initials: G
authors.lastname: Lepeu
authors.forename: B
authors.initials: B
authors.lastname: Dreyfus
authors.forename: J L
authors.initials: JL
authors.lastname: Binet
authors.forename: P
authors.initials: P
authors.lastname: Travade
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002699:Chlorambucil / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002699:Chlorambucil; D011241:Prednisone