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Anthracycline-Induced Clinical Heart Failure in a Cohort of 607 Children: Long-Term Follow-Up Study

From the Departments of Pediatric Oncology, Pediatric Cardiology, and General Pediatrics, Academic Medical Center, Emma Kinder Ziekenhuis, University of Amsterdam, Amsterdam, the Netherlands.

Address reprint requests to L.C.M. Kremer, MD, Department of Pediatrics, Emma Kinder Ziekenhuis, Academic Medical Center, University of Amsterdam, G8-259, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; email L.C.Kremer{at}AMC.UVA.NL

PURPOSE: To determine the early and late cumulative incidence of anthracycline-induced clinical heart failure (A-CHF) after anthracycline therapy in childhood and to identify associated risk factors.

PATIENTS AND METHODS: The cumulative incidence of A-CHF and the risk factors of A-CHF were assessed in a cohort of 607 children who had been treated with anthracyclines between 1976 and 1996. For 96% of the cohort, we obtained the clinical status up to at least January 1997. The mean follow-up time was 6.3 years.

RESULTS: The cumulative incidence of A-CHF was 2.8%, after a mean follow-up time of 6.3 years and a mean cumulative dose of anthracyclines of 301 mg/m². A cumulative dose of anthracycline higher than 300 mg/m² was associated with an increased risk of A-CHF (relative risk, 11.8; 95% confidence interval, 1.6 to 59.5) compared with a cumulative dose lower than 300 mg/m². The estimated risk of A-CHF increased with time after the start of anthracycline chemotherapy to 2% after 2 years and 5% after 15 years.

CONCLUSION: Up to 5% of patients will develop A-CHF 15 years after treatment, and patients treated with a cumulative dose of anthracyclines higher than 300 mg/m² are at highest risk for A-CHF. This is thus a considerable and serious problem among these young patients. The findings reinforce the need for strategies for early detection of patients at risk for A-CHF and for the evaluation of other chemotherapeutic possibilities or cardioprotective agents in relation to the survival.

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