Longitudinal evaluation of early and late anthracycline cardiotoxicity in children with AML

Pediatr Blood Cancer. 2007 Jun 15;48(7):651-62. doi: 10.1002/pbc.21105.


Background: Anthracyclines are effective antineoplastic drugs in acute myelogenous leukemia (AML). However, their use is limited by cardiomyopathy, which occurs in children already at cumulative doses of 300 mg/m(2) (given as daunorubicin equivalent).

Procedure: To evaluate anthracycline-associated cardiomyopathy in pediatric AML-patients, the incidence of early and late (>1 year after intensive AML chemotherapy) clinical and subclinical cardiotoxicity was analyzed out of a total of 1,207 patients <18 years treated between 1993 and 2003 in trials AML-BFM93/98: 1,010 protocol patients with de novo AML, 121 with Down syndrome (DS)-AML, and 76 with secondary AML. The cumulative dose of anthracyclines was generally risk-adapted: 300-450 mg/m(2) using 1-4-hr infusions of anthracyclines with the assumed lowest cardiotoxic potential. Eight hundred eighty-five patients (73%) were eligible for the analysis of early and 547 (45%) of late cardiotoxicity (1,399 follow-up data).

Results: Thirty-eight patients (4.3%), including 3 DS-AML and 1 secondary AML, suffered from early cardiomyopathy. After 5 years, four patients showed temporarily or persistently a reduced shortening fraction, which led to death in one DS-AML patient. Including these 4 patients, late cardiomyopathy was seen in 16 patients (cumulative incidence after 11 years: 5% +/- 1%). Nine patients (2.5 +/- 1%) showed clinical symptoms, five of them had persistent abnormal shortening fraction. Late subclinical cardiomyopathy occurred temporarily in seven patients. Late clinical cardiomyopathy mainly affected patients with a second anthracycline therapy (secondary malignancy) and those with early cardiotoxicity.

Conclusion: In spite of a highly intensive and effective treatment, the frequency of anthracycline-associated cardiomyopathy was low in the AML-BFM studies.

Publication types

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

MeSH terms

  • Acute Disease
  • Adolescent
  • Anthracyclines / administration & dosage
  • Anthracyclines / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Drug-Related Side Effects and Adverse Reactions
  • Echocardiography / methods
  • Female
  • Follow-Up Studies
  • Heart / drug effects*
  • Heart Diseases / chemically induced*
  • Heart Diseases / diagnostic imaging
  • Humans
  • Infant
  • Leukemia, Myeloid / diagnosis
  • Leukemia, Myeloid / drug therapy*
  • Longitudinal Studies
  • Male
  • Pilot Projects
  • Risk Factors
  • Survivors
  • Time
  • Treatment Outcome


  • Anthracyclines