Risk Factors Associated with Anthracycline Induced Cardiac Dysfunction in Pediatric Patients

Abstract

Objectives: To identify risk factors for anthracycline induced acute (within one month) and early onset chronic progressive (within year) cardiotoxicity. Patients and Methods: This prospective cohort study enrolled all children who received anthracycline chemotherapy for different malignancies and three echocardiographic evaluations (baseline, one month and 1 year) between July 2010 and June 2012. Results: 110 children (aged 1 month to 16 years) were included. Mean age was 74 ± 44 months and 75 (68.2%) were males. Acute lymphoblastic leukemia (ALL) was seen in 70 (64%) patients. Doxorubicin alone was used in 59 (54%) and combination therapy in 35(32%). A cumulative dose of anthracycline < 300mg/m2 was in 95 (86%). Fifteen (14%) children developed cardiac dysfunction within a month and 28(25%) children within a year. Of these 10/15 (66.6%) and 12/28 (43%) had isolated diastolic dysfunction respectively, while 5/15 (33.3%) and 16/28 (57%) had combined systolic and diastolic dysfunction. Seven (6.4%) patients succumbed to cardiac dysfunction. 8/59 (13.5%) children showed dysfunction due to high cumulative dose (p = < 0.001). Cardiotoxicity was higher with combination of doxorubicin and daunorubicin (p = 0.004), when bolus rather than infusion therapy was given (p = 0.04), with radiation therapy (p = 0.009) and sepsis (p = 0.002). Down syndrome, Ewing's sarcoma and acute myeloid leukemia had higher cardiotoxicity, but did not reach statistical significance. Conclusion: Anthracyclines caused cardiac dysfunction with high cumulative dose, more with doxorubicin, sepsis, radiation and bolus drug administration. Improved outcome relates to early identification and treatment and long term follow-up to address late manifestations.