Anthracycline-induced clinical heart failure in a cohort of 607 children: long-term follow-up study.
OBJECTIVE
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.


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/m(2). A cumulative dose of anthracycline higher than 300 mg/m(2) 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/m(2). 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.


CONCLUSIONS
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/m(2) 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.
Kremer
L C
LC
Department of Pediatric Oncology, Academic Medical Center, Emma Kinder Ziekenhuis, University of Amsterdam, Amsterdam, The Netherlands. L.C.Kremer@AMC.UVA.NL
van Dalen
E C
EC
Offringa
M
M
Ottenkamp
J
J
Voûte
P A
PA
D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000139:chemically induced* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D009369:Neoplasms / Q000188:drug therapy*; D009426:Netherlands / Q000453:epidemiology; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis
D000903:Antibiotics, Antineoplastic