title: Vinblastine in children and adolescents with high-risk anaplastic large-cell lymphoma: results of the randomized ALCL99-vinblastine trial.
abstract: OBJECTIVE
  The impact of adding vinblastine to a 4-month chemotherapy regimen, based on the Non-Hodgkin's Lymphoma Berlin-Frankfurt-Münster 90 protocol, in childhood high-risk anaplastic large-cell lymphoma (ALCL) was assessed.
  
  
  METHODS
  Children and adolescents with high-risk ALCL, defined by mediastinal, lung, liver, spleen, or skin involvement, were eligible for the trial. After a prephase and one chemotherapy course, patients were randomly assigned to receive either five further chemotherapy courses without vinblastine or the same regimen with one vinblastine injection (6 mg/m(2)) during each course followed by weekly vinblastine to complete a total of 1 year of treatment. The primary end point was event-free survival (EFS), analyzed on the intent-to-treat population.
  
  
  RESULTS
  Between November 1999 and June 2006, 110 patients were randomly assigned to receive vinblastine, and 107 were randomly assigned not to receive vinblastine. Median follow-up was 4.8 years. Patients in the vinblastine arm had a significantly reduced risk of events during the first year (hazard ratio [HR] = 0.31; 95% CI, 0.15 to 0.67; P = .002) followed by an increased risk thereafter (HR = 4.98; 95% CI, 1.65 to 15.0; P = .003). Consequently, EFS at 1 year differed significantly (91% in the vinblastine group v 74% in the no-vinblastine group), with no difference at 2 years (73% and 70%, respectively). Overall EFS curves did not differ significantly (HR = 0.91; 95% CI, 0.55 to 1.5; P = .71). Thirty-one percent of weekly doses of vinblastine were reduced as a result of hematologic toxicity, although vinblastine was discontinued for toxicity in only three patients.
  
  
  CONCLUSIONS
  Adding vinblastine during induction and as maintenance for a total treatment duration of 1 year significantly delayed the occurrence of relapses but did not reduce the risk of failure.
authors.affiliation: Biostatistics and Epidemiology Unit, Institut Gustave-Roussy, Villejuif, France. marie-cecile.ledeley@igr.fr
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Le Deley
authors.forename: Angelo
authors.initials: A
authors.lastname: Rosolen
authors.forename: Denise M
authors.initials: DM
authors.lastname: Williams
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
authors.forename: Grazyna
authors.initials: G
authors.lastname: Wrobel
authors.forename: Andishe
authors.initials: A
authors.lastname: Attarbaschi
authors.forename: Jozsef
authors.initials: J
authors.lastname: Zsiros
authors.forename: Anne
authors.initials: A
authors.lastname: Uyttebroeck
authors.forename: Ildiko M
authors.initials: IM
authors.lastname: Marky
authors.forename: Laurence
authors.initials: L
authors.lastname: Lamant
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Woessmann
authors.forename: Marta
authors.initials: M
authors.lastname: Pillon
authors.forename: Rachel
authors.initials: R
authors.lastname: Hobson
authors.forename: Audrey
authors.initials: A
authors.lastname: Mauguen
authors.forename: Alfred
authors.initials: A
authors.lastname: Reiter
authors.forename: Laurence
authors.initials: L
authors.lastname: Brugières
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D018572:Disease-Free Survival; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy; D014747:Vinblastine / Q000008:administration & dosage*
chemical_list: D014747:Vinblastine