An expert opinion on pharmacologic approaches to reducing the cardiotoxicity of childhood acute lymphoblastic leukemia therapies

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children. Treatment-related cardiac damage is progressive and often difficult to reverse. Strategies to minimize cardiotoxicity during treatment are crucial to prevent severe lasting effects on health and quality of life. AREAS COVERED: This comprehensive review covers the pathophysiology and various presentations, both clinical and subclinical, of treatment-induced cardiotoxicity and characteristics associated with increased risk of cardiac dysfunction in childhood ALL survivors. Additionally, contemporary prevention strategies such as limiting cumulative anthracycline dose, altering drug administration schedule, the use of anthracycline structural analogs, liposomal encapsulated anthracyclines, cardioprotective agents and nutritional supplements are critically analyzed. Finally, this review covers the management options of chemotherapy-induced damage and other treatment-related cardiotoxicity. EXPERT OPINION: Higher lifetime cumulative doses of anthracyclines, younger age at diagnosis, longer follow-up, female sex, higher dose rates and cranial irradiation are associated with more severe cardiotoxic effects. Long-term adverse effects of both anthracycline and non-anthracycline chemotherapeutic agents are becoming an increasing focus during treatment of childhood malignancies. There must be a careful balance between achieving remission of childhood ALL while avoiding the development of another often-fatal illness, heart failure.