Repetitive cycles of high-dose cytarabine are effective for childhood acute myeloid leukemia: long-term outcome of the children with AML treated on two consecutive trials of Tokyo Children's Cancer Study Group

Pediatr Blood Cancer. 2007 Aug;49(2):127-32. doi: 10.1002/pbc.20944.

Abstract

Background: Various methods of intensive chemotherapy have contributed to an improved survival in pediatric acute myeloid leukemia (AML). We here report the long-term results of the two consecutive trials of Tokyo Children's Cancer Study Group (TCCSG), incorporating repetitive use of high-dose cytarabine (HD-Ara-C) based combination chemotherapy in post-remission phase.

Procedure: A total of 216 eligible children with newly diagnosed AML were treated in the two consecutive multi-center trials of TCCSG, M91-13 and M96-14, from August 1991 to September 1998. In M91-13 trial, patients received eight courses of intensive post-remission chemotherapy, including six HD-Ara-C containing courses, after remission-induction therapy. Autologous hematopoietic stem cell transplantation (HSCT) could be selected by physician's choice, and allogeneic HSCT was allocated if donor was available. In M96-14 trial, the last two HD-Ara-C courses were omitted from the chemotherapy arm.

Results: The remission-induction rate was 88.8% and probability of 5-year Overall survival (OS) and event-free survival (EFS) were 62% (56-69% with 95% Confidence intervals (CIs)) and 56% (49-62%), respectively. Treatment-related mortality (TRM) was 7.8%. Among patients without Down syndrome (DS) or acute promyelocytic leukemia (APL), the presence of t(8;21) or inv(16) was a significant good prognostic factor both in the univariate and multivariate analyses. Children with DS (N = 10) and APL (N = 14) also showed a good survival exceeding 70% in 5 years.

Conclusions: These results suggest that repetitive use of HD-Ara-C was effective and safe for childhood AML. However, further optimization of AML therapy is required.

Publication types

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

MeSH terms

  • Acute Disease
  • Adolescent
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Cytarabine / administration & dosage
  • Cytarabine / therapeutic use
  • Disease-Free Survival
  • Down Syndrome / complications
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Drug Administration Schedule
  • Etoposide / administration & dosage
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Hydrocortisone / administration & dosage
  • Infant
  • Infections / etiology
  • Infections / mortality
  • Japan / epidemiology
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / surgery
  • Male
  • Methotrexate / administration & dosage
  • Mitoxantrone / administration & dosage
  • Remission Induction
  • Survival Analysis
  • Transplantation, Autologous
  • Transplantation, Homologous
  • Treatment Outcome
  • Tretinoin / administration & dosage
  • Vincristine / administration & dosage

Substances

  • Antimetabolites, Antineoplastic
  • Cytarabine
  • Tretinoin
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Mitoxantrone
  • pirarubicin
  • Hydrocortisone
  • Methotrexate