Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia, 1984-1999

Leukemia. 2010 Feb;24(2):383-96. doi: 10.1038/leu.2009.260. Epub 2009 Dec 24.


We report the long-term results of Tokyo Children's Cancer Study Group's studies L84-11, L89-12, L92-13, and L95-14 for 1846 children with acute lymphoblastic leukemia, which were conducted between 1984 and 1999. The value of event-free survival (EFS)+/-s.e. was 67.2+/-2.2% at 10 years in L84-11, which was not improved in the following two studies, and eventually improved to 75.0+/-1.8% at 10 years in L95-14 study. The lower EFS of the L89-12 reflected a high rate of induction failure because of infection and delayed remission in very high-risk patients. The L92-13 study was characterized by short maintenance therapy; it resulted in poor EFS, particularly in the standard-risk (SR) group and boys. Females did significantly better than males in EFS in the early three studies. The gender difference was not significant in overall survival, partly because >60% of the males survived after the testicular relapse. Randomized studies in the former three protocols revealed that intermediate- or high-dose methotrexate therapy significantly reduced the testicular relapse rate. In the L95-14 study, gender difference disappeared in EFS. Contrary to the results of larger-scale studies, the randomized control study in the L95-14 reconfirmed with updated data that dexamethasone 8 mg/m(2) had no advantage over prednisolone 60 mg/m(2) in the SR and intermediate-risk groups. Prophylactic cranial irradiation was assigned to 100, 80, 44, and 44% of the patients in the studies, respectively. Isolated central nervous system relapse rates decreased to <2% in the last two trials. Secondary brain tumors developed in 12 patients at 8-22 years after cranial irradiation. Improvement of the remission induction rates and the complete omission of irradiation are currently main objectives in our studies.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Child, Preschool
  • Chromosome Aberrations
  • Combined Modality Therapy
  • Cranial Irradiation*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunophenotyping
  • Infant
  • Japan
  • Male
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • Neoplasm, Residual
  • Neoplasms, Second Primary / genetics
  • Neoplasms, Second Primary / pathology
  • Neoplasms, Second Primary / therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Prognosis
  • Remission Induction
  • Risk Factors
  • Survival Rate
  • Time Factors
  • Treatment Outcome