Early cardiac outcomes following contemporary treatment for childhood acute myeloid leukemia: a North American perspective

Pediatr Blood Cancer. 2013 Sep;60(9):1528-33. doi: 10.1002/pbc.24498. Epub 2013 Feb 25.

Abstract

Background: Anthracycline agents are used for treatment of acute myeloid leukemia (AML) but may cause late-onset cardiomyopathy. Current frontline therapy for AML in North America, as reflected in the approach of the Children's Oncology Group (COG) and other pediatric consortia, is adapted from the anthracyline-intensive Medical Research Council (MRC) regimen. The purpose of this study was to describe early post-treatment cardiac function as a potential indicator of acute and long-term risk associated with this approach.

Procedure: A multi-center retrospective cohort analysis was conducted of AML survivors diagnosed from 2004 to 2009 and treated with MRC-based regimens. Change in left ventricular shortening fraction (LVSF) on echocardiogram was determined from baseline to latest post-treatment/pre-relapse value; associations with potential predictors were examined.

Results: This cohort of pediatric survivors (n = 52) was assessed at a median interval of 13 months from end of treatment. Mean cumulative anthracycline dose was 339 ± 14 mg/m(2) . Mean baseline and post-treatment LVSF were 39.3 ± 0.8% and 35.4 ± 0.9%, respectively; mean percent change for individuals was -8.4 ± 2.8% (P < 0.001). Cardiac-directed medications were initiated in four patients (7.7%). Decline in LVSF was significantly associated with cumulative anthracycline dose, increasing BMI and Hispanic ethnicity.

Conclusion: Early, significant decline in LVSF was observed following treatment with these MRC-based regimens. Elevated BMI and Hispanic ethnicity were identified as new independent risk factors. Children and adolescents so treated are at substantial risk for late-onset cardiomyopathy, require monitoring with annual echocardiogram per current COG survivorship guidelines, and are good candidates for appropriate cardioprotection strategies.

Keywords: AML; cardiotoxicity; late effects.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Anthracyclines / administration & dosage
  • Anthracyclines / adverse effects*
  • Cardiomyopathies / chemically induced*
  • Cardiomyopathies / mortality
  • Cardiomyopathies / physiopathology*
  • Child
  • Child, Preschool
  • Echocardiography
  • Female
  • Hispanic or Latino
  • Humans
  • Infant
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / physiopathology*
  • Male
  • Retrospective Studies
  • Risk Factors
  • Survival Rate
  • United States
  • Ventricular Remodeling / drug effects*

Substances

  • Anthracyclines