Effect of Early Cardiotoxicity on Outcomes in Pediatric AML


Key Points

  • Most cardiotoxicity occurred during on-protocol treatment.
  • Cardiotoxicity was associated with poorer event-free and overall survival.

In an analysis from the Children’s Oncology Group AAML0531 trial reported in the Journal of Clinical Oncology, Getz et al found that early treatment-related cardiotoxicity may be associated with poorer event-free and overall survival in pediatric acute myeloid leukemia (AML).

Study Details

The study involved data from 1,022 patients aged < 30 years (55% aged < 10 years) receiving front-line treatment with daunorubicin and mitoxantrone for AML. Cardiotoxicity was evaluated via adverse event monitoring during follow-up, and was defined as grade 2 or higher left ventricular systolic dysfunction. Data in the current analysis were current as of September 2016, with a median follow-up of 6.6 years among patients alive at last contact.

Cardiotoxicity and Outcomes

Over 5-year follow-up, 12% of patients had cardiotoxicity, with more than 70% of incident events occurring during on-protocol treatment. Median time to cardiotoxicity was 4.3 months. Overall, 25% of incident events were associated with infection. Cardiotoxicity during on-protocol treatment was significantly associated with later occurrence of off-protocol toxicity. The 5-year incidence was higher among noninfants and black patients, as well as in patients with bloodstream infection.

Patients with cardiotoxicity had significantly poorer 5-year event-free survival (hazard ratio [HR] = 1.57, P = .004) and overall survival (HR = 1.59, P = .005). The effects on event-free survival were similar for infection-associated cardiotoxicity (36.5% vs 50.0%, HR = 1.62, P = .069) and cardiotoxicity in the absence of infection (32.8% vs 50.0%, HR = 1.55, P = .017) vs patients without cardiotoxicity. For overall survival, effects differed somewhat among patients with cardiotoxicity without infection (45.1% vs 66.0%, HR = 1.72, P = .004) and among those with infection-associated cardiotoxicity (56.7% vs 66.0%, HR = 1.30, P = .387) vs patients without cardiotoxicity.

The investigators concluded, “Early treatment-related cardiotoxicity may be associated with decreased [event-free survival] and [overall survival]. Cardioprotective strategies are urgently needed to improve relapse risk and both short- and long-term mortality outcomes.”

The trial was supported by National Clinical Trials Network Operations Center and National Clinical Trials Network Statistics & Data Center grants from the National Cancer Institute and St Baldrick’s Foundation.

Kelly D. Getz, PhD, of the Perelman School of Medicine, University of Pennsylvania, is the corresponding author for the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.