Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children's Cancer Group

Blood. 2003 May 15;101(10):3809-17. doi: 10.1182/blood-2002-08-2454. Epub 2003 Jan 16.

Abstract

Conventional therapy for childhood acute lymphoblastic leukemia (ALL) includes prednisone and oral 6-mercaptopurine. Prior observations suggested potential advantages for dexamethasone over prednisone and for intravenous (IV) over oral 6-mercaptopurine, which remain to be validated. We report the results of a randomized trial of more than 1000 subjects that examined the efficacy of dexamethasone and IV 6-mercaptopurine. Children with National Cancer Institute standard-risk ALL were randomly assigned in a 2 x 2 factorial design to receive dexamethasone (6 mg/m(2)/d) for 28 days in induction, plus taper, compared with prednisone (40 mg/m(2)/d). The second randomized assignment was for daily oral or weekly IV 6-mercaptopurine during consolidation. During maintenance, 5 days of the randomized steroid was given monthly, at the same dose, and all patients received daily oral 6-mercaptopurine. During delayed intensification, all patients received a dexamethasone dosage of 10 mg/m(2)/d for 21 days, with taper. Intrathecal (IT) methotrexate was the sole central nervous system-directed therapy. Patients randomly assigned to receive dexamethasone had a 6-year isolated central nervous system-relapse rate of 3.7% +/- 0.8%, compared with 7.1% +/- 1.1% for prednisone (P =.01). There was also a trend toward fewer isolated bone marrow relapses with dexamethasone. The 6-year event-free survival (EFS) was 85% +/- 2% for dexamethasone and 77% +/- 2% for prednisone (P =.002). EFS was similar with oral or IV 6-mercaptopurine; however, patients assigned to IV 6-mercaptopurine had decreased survival after relapse.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use
  • Blood Cell Count
  • Child
  • Child, Preschool
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Dexamethasone / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Humans
  • Infant
  • Injections, Intravenous
  • Injections, Spinal
  • Karyotyping
  • Male
  • Mercaptopurine / administration & dosage
  • Mercaptopurine / adverse effects
  • Mercaptopurine / therapeutic use*
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Prednisone / administration & dosage
  • Prednisone / adverse effects
  • Prednisone / therapeutic use*

Substances

  • Antimetabolites, Antineoplastic
  • Dexamethasone
  • Mercaptopurine
  • Prednisone
  • Methotrexate