title: Pulses of vincristine and dexamethasone in addition to intensive chemotherapy for children with intermediate-risk acute lymphoblastic leukaemia: a multicentre randomised trial.
abstract: BACKGROUND
  Studies in the 1970s and 1980s suggested that the outcome of childhood acute lymphoblastic leukaemia (ALL) could be improved by intensification of conventional continuation chemotherapy with pulses of vincristine sulfate and steroids. We aimed to investigate the efficacy and toxic effects of vincristine-dexamethasone pulses as an addition to the continuation-therapy phase in a large cohort of children with intermediate-risk disease who were treated with the Berlin-Frankfurt-Münster (BFM) treatment strategy.
  
  
  METHODS
  3109 children, diagnosed with ALL and intermediate-risk features, were enrolled by eight participating organisations in eleven countries. All were treated with very similar protocols based on the BFM treatment strategy, which included induction, consolidation, reinduction, and continuation-therapy phases. At the beginning of the continuation-therapy phase, those patients in complete remission were randomly assigned to either a treatment or a control group. Control patients were given conventional mercaptopurine and methotrexate chemotherapy only. Patients in the treatment arm were also given pulses of vincristine (1.5 mg/m2 weekly for 2 weeks) and dexamethasone (6 mg/m2 daily for 7 days) every 10 weeks for six cycles. The primary outcome measure was disease-free survival. Analysis was by intention to treat. The study is registered at http://www.clinicaltrials.gov with the identifier NCT00411541.
  
  
  RESULTS
  174 patients (5.6%) relapsed or died in complete remission before randomisation. Of the remaining 2935 patients, 2618 (89.2%) were randomly assigned: 1325 to the treatment group and 1293 to the control group. With median follow-up of 4.8 years, 240 children in the treatment group and 241 in the control group had relapses; 15 in the treatment group and 14 controls died in complete remission or developed second malignant neoplasms. The 5-year and 7-year disease-free survival estimates were 79.8% (SE 1.2) and 77.5% (1.5) in the treatment group and 79.2% (1.2) and 78.4% (1.3) in the control group, respectively. Treatment with pulses of vincristine and dexamethasone was associated with a non-significant 3% relative-risk reduction (hazard ratio 0.97; 95% CI 0.81-1.15; p=0.70).
  
  
  CONCLUSIONS
  Children with intermediate-risk ALL who received intensive chemotherapy based on BFM protocols did not benefit from intensification of the continuation-therapy phase with a schedule of pulses of vincristine and dexamethasone.
authors.affiliation: Department of Paediatrics, University of Milano-Bicocca, Ospedale San Gerardo, Monza, Italy. valentino.conter@pediatriamonza.it
authors.forename: Valentino
authors.initials: V
authors.lastname: Conter
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.forename: Daniela
authors.initials: D
authors.lastname: Silvestri
authors.forename: Myriam
authors.initials: M
authors.lastname: Campbell
authors.forename: Eduardo
authors.initials: E
authors.lastname: Dibar
authors.forename: Edina
authors.initials: E
authors.lastname: Magyarosy
authors.forename: Helmut
authors.initials: H
authors.lastname: Gadner
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Yves
authors.initials: Y
authors.lastname: Benoit
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Alfred
authors.initials: A
authors.lastname: Reiter
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Riehm
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Masera
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
mesh_terms: D000293:Adolescent; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014750:Vincristine; D003907:Dexamethasone; D015122:Mercaptopurine; D008727:Methotrexate