RISK-FACTORS FOR EARLY ANTHRACYCLINE CLINICAL CARDIOTOXICITY IN CHILDREN - THE PEDIATRIC-ONCOLOGY-GROUP EXPERIENCE

Purpose: To evaluate risk factors for clinical cardiotoxicity from ant hracycline chemotherapy in children with cancer and to estimate the re lative risk associated with each factor singly and with different comb inations of risk factors. Patients and Methods: The study population c onsisted of 6493 children with cancer who had received anthracycline c hemotherapy on Pediatric Oncology Group protocols during the period fr om 1974 to 1990. Cardiotoxicity, defined as congestive heart failure n ot due to other causes, abnormal measurements of cardiac function that prompted the discontinuation of therapy, or sudden death from presume d cardiac causes, was determined by a review of protocol records. Resu lts: Cardiotoxicity was confirmed in 106 patients (1.6%): 58 had conge stive heart failure, 43 had changes in measures of cardiac function th at prompted the discontinuation of therapy and five died suddenly from presumed cardiac causes. In a multivariate analysis, factors contribu ting to the relative risk (RR) of toxicity were a cumulative dose of a nthracycline greater than or equal to 550 mg/m(2) of body-surface area (RR = 5.2), a maximal dose of 50 mg/m(2) (RR = 2.8), female sex (RR = 1.9), black race (RR = 1.7), the presence of trisomy 21 (RR = 3.4) an d exposure to amsacrine (RR = 2.6). The relative risk of early clinica l cardiotoxicity increased with increasing numbers of risk factors and was projected to exceed 405 when all six statistically significant ri sk factors were present. Conclusion: Early clinical cardiotoxicity in children treated with anthracycline is rare. A high maximal dose, or c umulative dose of anthracycline, female sex, black race, the presence of trisomy 21 and treatment with amsacrine increase the risk for anthr acycline-associated cardiotoxicity. The cumulative effect of multiple risk factors can be estimated as the product of the relative risks ass ociated with each. (C) 1998 Elsevier Science Ireland Ltd.