Seattle Children's Hospital
Project Term: July 1, 2019 - June 30, 2024
We seek to reduce the adverse cardiac effects of chemotherapy in pediatric AML patients. We are assessing markers of heart function and injury to compare two clinical strategies for prevention of chemotherapy-induced heart injury. We are also developing a tool using these markers of heart function to characterize a child’s risk for cardiac dysfunction, which is critical to guiding safe chemotherapy delivery. By reducing the toxicity of therapy on the heart we hope to optimize delivery of effective chemotherapy and contribute to long-term leukemia cure without the burden of life-threatening heart disease during survivorship.
This project aims to find successful strategies to reduce the impact of acute myeloid leukemia (AML) therapy on the heart. AML is a cancer of white blood cells that is exceedingly difficult to treat and requires highly intensive chemotherapy. Unfortunately, the cost of cure is high; many patients who survive their cancer develop life-threatening heart disease from their chemotherapy. Patients who experience poor heart function during or soon after leukemia therapy not only have a higher risk for long-term heart problems but also have higher rates of leukemia relapse and death. An upcoming Children’s Oncology Group trial for pediatric AML will compare two strategies for protecting the heart during intensive anthracycline-containing chemotherapy. Half of the patients treated on this study will receive standard AML therapy with dexrazoxane, a drug that helps prevent anthracycline-induced injury to the heart. The other half of patients will receive CPX-351, a formulation of anthracycline (and another chemotherapy drug, cytarabine) enclosed within a liposomal capsule that limits the drug’s ability to get into the heart and cause injury. While the main goal of this trial is to improve the effectiveness of therapy in curing leukemia, it is critically important to determine how well these therapies protect the heart. Therefore, the first objective of this research study is to compare sensitive imaging markers of cardiac function by echocardiogram across treatment arms in order to identify the most effective strategy for reducing chemotherapy-induced cardiotoxicity. Second, we will evaluate whether these sensitive imaging markers help to identify children at highest risk for subsequent cardiac dysfunction. Finally, we will generate an algorithm incorporating these early imaging markers of heart injury with clinical and treatment factors in order to evaluate each patient’s risk for cardiac dysfunction. Early insight into a child’s risk for cardiac disease following AML therapy would guide oncologists in making decisions about chemotherapy modifications and allow early initiation of cardiac medications aimed at preserving heart function and maintain the long-term cardiovascular health of AML survivors. In summary, this study is critical to determining the optimal strategy for reducing the side effects of AML therapy on the heart, which will allow us to not only cure children with AML but also to minimize the burden of late effects in AML survivors.