by Trish Adkins

ALSF-funded researcher (Innovation Grant 2009 and Epidemiology Grant 2013) Dr. Richard Aplenc of Children’s Hospital of Philadelphia is working to understand the underlying causes of cardiac dysfunction in children battling acute myeloid leukemia (AML). Five ALSF –funded POST Grant students have also worked on this research in the Aplenc Lab: Yang Ding, Alexandra Blumer, Joe Horowitz, Julianna Mann and Elizabeth Goodman. 

In the treatment of acute myeloid leukemia (AML), most cardiac side effects come from a type of chemotherapy called anthracyclines. Anthracyclines are used pretty extensively in treating pediatric cancer. In general, the more doses of anthracyclines a child receives, the greater the risk of long-term side effects, such as cardiac dysfunction. These long-term side effects of anthracyclines have been researched extensively. However, the short-term cardiac side effects, which can affect some children during treatment, have been less researched. 

ALSF-funded researcher and Scientific Review Board member Dr. Richard Aplenc is working to understand the underlying causes of short-term cardiac dysfunction. These side effects could happen immediately or within the first year of treatment with anthracyclines in children battling AML, a form of leukemia that requires more intensive chemotherapy.

Dr. Aplenc’s lab is working on a genome-wide genotyping effort to discover the genetic variations that change the risks of relapse, life-threatening infections and heart complications in these children. He also leads several efforts to use administrative data and sets out to improve the care of children with AML, particularly focusing on antibiotic and intensive care use.

Long-term cardiac side effects of anthracycline treatment can include an increased risk of heart attack and cardiomyopathy. In the short term, heart attacks do not happen, but some children experience cardiomyopathy, which is a dysfunction of the heart muscle. The heart muscle does not squeeze effectively, which can lead to a myriad of problems including congestive heart failure. This short-term side effect can lead to treatment delays, jeopardizing its effectiveness.

Dr. Aplenc is also studying the link between blood infections and short-term side effects of anthracycline treatment in children battling AML. Blood infections can also trigger cardiomyopathy. However, this link is poorly understood. 

The first part of his research will:

• Define the clinical experience of children with AML who experience a decrease in heart functions
• Define the cardiac risk factors in kids who have a blood infection versus those who do not have a blood infection
• Understand the pathophysiology that leads children with an infection to have a worse infection
• Determine if decreased heart function affects the risk of AML relapse 

The second part of his research is using DNA sequencing to understand if changes in a patient’s DNA could be related to their risk of cardiac side effects. 

“I want to be able to provide patients and their families with accurate estimates of cardiac toxicity risks in AML, so when a physician sits down with a family, they can accurately predict treatment outcomes and manage risk,” said Dr. Aplenc.