No impact of high-dose cytarabine and asparaginase as early intensification with intermediate-risk paediatric acute lymphoblastic leukaemia: results of randomized trial TCCSG study L99-15

Br J Haematol. 2014 Feb;164(3):376-83. doi: 10.1111/bjh.12632. Epub 2013 Oct 26.

Abstract

The Tokyo Children's Cancer Study Group conducted a randomized controlled study to evaluate the effect of experimental early intensification using high-dose cytarabine and L-asparaginase in paediatric intermediate-risk (IR) acute lymphoblastic leukaemia (ALL). A total of 310 IR ALL patients were randomized to receive either experimental early intensification (n = 156) or standard early intensification including standard-dose cytarabine arm (n = 154) after induction therapy. The experimental arm consisted of high-dose cytarabine and L-asparaginase, while the standard arm consisted of standard-dose cytarabine, oral 6-mercaptopurine and cyclophosphamide. The probabilities of event-free survival at 8 years in the experimental and standard arms were 72·3 ± 3·7% and 77·5 ± 3·5%, respectively (P = 0·32). The 8-year overall survival rates for these two arms were 85·0 ± 3·0% and 86·9 ± 2·8%, respectively (P = 0·72). The frequency of infectious events was significantly higher in the experimental arm (66·4%) than in the standard arm (24·6%) (P < 0·001). In conclusion, experimental early intensification including high-dose cytarabine followed by L-asparaginase had no advantage over standard early intensification in paediatric IR ALL patients.

Keywords: acute lymphoblastic leukaemia; child; early intensification; high-dose cytarabine; randomized trial.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / administration & dosage
  • Child
  • Child, Preschool
  • Cytarabine / administration & dosage
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infant
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Remission Induction
  • Risk Factors
  • Survival Rate
  • Treatment Outcome

Substances

  • Cytarabine
  • Asparaginase