Smita Bhatia, M.D., MPH, director of the Institute for Cancer Outcomes and Survivorship, has been awarded a $600,000 grant by the Leukemia and Lymphoma Society to study anthracycline-related cardiotoxicity in childhood cancer survivors.
Anthracycline chemotherapies are critical treatments used for children with leukemia and lymphoma. However, these chemotherapies have a widely known side effect of dose-dependent risk of cardiac dysfunction (CD) progressing to congestive heart failure (CHF). Childhood cancer survivors have a 5 to 15 times greater risk of heart failure than the general population. An inter-patient variability in CD/CHF risk for any given dose of anthracyclines suggests there is a genetic predisposition to how an individual handles anthracyclines and how the heart responds to the chemotherapy. There is a critical need to identify children diagnosed with leukemia or lymphoma who are at the highest risk of heart failure so targeted interventions can be instituted.
The project funded by this grant will merge concepts from molecular biology and cancer survivorship to understand the pathogenesis of anthracycline-related cardiotoxicity and identify individuals by their personal risk of anthracycline-related cardiotoxicity. A risk prediction model, using a patient’s genetic make-up, clinical characteristics and treatment exposure, will be developed and used to determine a patient’s risk of heart failure. After the molecular basis of anthracycline-related heart failure is determined, a clinical plus genetic risk prediction model can be created to identify children diagnosed with leukemia or lymphoma who are at a higher risk of heart failure. When this model is applied to newly diagnosed patients with hematologic malignancies, personalized interventions can be implemented to reduce the risk of morbidity due to heart failure and optimize cancer-free survival.
“This study will inform the practice of personalized medicine in children with cancer, with the ultimate goal of maximizing cure while simultaneously minimizing long-term toxicity,” explained Bhatia.