Abstract 9749: Anthracicline-Induced Cardiotoxicity in Children. Pharmacogenetics and Clinical Study at a Tertiary Center

Abstract

Introduction: Children and adolescents treated with anthracyclines are at increased risk of developing cardiomyopathy. Although several guidelines are available, no consensus exists on an optimal strategy scheme for predict or avoid anthracycline-induced cardiotoxicity. Methods: Cardiotoxicity was defined as a reduction in left ventricle ejection fraction >10% from baseline and <53%, and/or global longitudinal strain drop of >15%.The incidence of cardiotoxicity, its relation with cumulative anthracycline doses, clinical significance and reversibility were retrospectively evaluated in a paediatric population (0-18 years) treated with anthracycline at a tertiary hospital (2010-2020). Analysis of 3 genetic polymorphisms related to cardiotoxicity (RARG (rs2229774), SLC28A3(rs7853758) and UGT1A6(rs17863783)) was performed. Results: A total of 84 patients (45 males) were included. The mean age at diagnosis was 10.7± 3.8 years with average cumulative anthracycline dose 195 mg/m2 (60-460mg/m2). Median follow-up was 5 years. Anthracycline-induced cardiotoxicity occurred in 12 (14,2%) of treated patients, 75% were asymptomatic. 5 patients experimented acute cardiotoxicity during treatment. 8 patients were treated with ACE-inhibitors and/or beta-blockers. 11 patients had full function recovery. Cumulative doxorubicin dose was a risk factor of cardiotoxicity, being affected 9/20 treated with >250 mg/m2; 3/51 treated with 100-250m2; while no patient out of 13 receiving <100 mg/m2 had an abnormal echocardiogram (P <0.01). A higher percentage of patients treated with mediastinum radiation and chemotherapy (3/7:42%) presented cardiotoxicity compared to those with chemotherapy only (9/77:9%) (p0.09). Younger age, female sex or the presence of genetic polymorphisms studied were not statistically significant risk factors. Conclusions: Dose-dependent anthracycline risk for developing cardiomyopathy was confirmed. However, previously identified risk factors including female sex, early age at diagnosis and genetic polymorphism were not replicated in this population, possibly due to the small sample size and the relatively short follow-up period. A tailored monitoring strategy based on cardiac risk stratification is needed.