Preserved High Probability of Overall Survival with Significant Reduction of Chemotherapy for Myeloid Leukemia in Down Syndrome: A Nationwide Prospective Study in Japan

Pediatr Blood Cancer. 2016 Feb;63(2):248-54. doi: 10.1002/pbc.25789. Epub 2015 Oct 20.

Abstract

Background: On the basis of results of previous Japanese trials for myeloid leukemia in Down syndrome (ML-DS), the efficacy of risk-oriented therapy was evaluated in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-D05 study.

Procedure: All patients received induction chemotherapy that consisted of pirarubicin, intermediate-dose cytarabine, and etoposide. Patients who achieved complete remission (CR) after initial induction therapy were stratified to the standard risk (SR) group and received four courses of reduced-dose intensification therapy. Patients who did not achieve CR were stratified to the high risk (HR) group and received intensified therapy that consisted of continuous or high-dose cytarabine.

Results: A total of 72 patients were eligible and evaluated. One patient died of sepsis during initial induction therapy. Sixty-nine patients were stratified to SR and two patients to HR. No therapy-related deaths were observed during intensification therapy. The 3-year event-free and overall survival rates were 83.3% ± 4.4% and 87.5% ± 3.9%, respectively. Age at diagnosis less than 2 years was a significant favorable prognostic factor for risk of relapse (P = 0.009).

Conclusions: The attempt of risk-oriented prospective study for ML-DS was unsuccessful, but despite the dose reduction of chemotherapeutic agents, the overall outcome was good, and further dose reduction might be possible for specific subgroups.

Keywords: Down syndrome; acute myeloid leukemia; clinical trial.

Publication types

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

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Child
  • Child, Preschool
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Disease-Free Survival
  • Down Syndrome / complications*
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Doxorubicin / analogs & derivatives
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Humans
  • Induction Chemotherapy / methods
  • Infant
  • Japan
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid / complications*
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / mortality
  • Male
  • Prospective Studies

Substances

  • Cytarabine
  • Etoposide
  • Doxorubicin
  • pirarubicin