Funded by the Dick Vitale Pediatric Cancer Research Fund
Anthracycline chemotherapy is used to treat over 50% of childhood cancer, and has resulted in improving in survival, such that over 85% of children now survive 5 or more years after a cancer diagnosis. Unfortunately, heart failure is an unwanted side-effect of anthracyclines, and is one of the leading causes of death in children cured of their cancer. Childhood cancer survivors are at a 5-15-fold higher risk of serious heart problems compared to the general population. The risk of heart failure increases with anthracycline dose, but the risk differs from child to child. Several studies have looked at the cause of heart failure at the DNA level. However, it is important to take this investigation to the next level, that is, truly understand the basic causes of at heart failure caused by anthracyclines. We propose to do this in a large study across 141 childhood cancer hospitals, where we are collecting blood samples from 300 childhood cancer survivors who have developed heart failure and 300 childhood cancer survivors who did not develop heart failure. We will use this information to get a deeper look at how anthracyclines cause heart failure. We hope that this will help us identify patients at highest risk, providing guidance in developing new ways to prevent and treat this unfortunate complication.
Funded by the Stuart Scott Memorial Cancer Research Fund
Stem cell transplantation is an effective way to treat patients with blood cancers. However, this treatment can cause short- and long-term side effects. These side effects may affect quality of life and increase risks for other diseases. Doctors must balance these risks with the potential for stem cell transplant to cure patients. A risk-prediction model can help with such decisions, but current models are inadequate. Risk-prediction models are often based on a patient’s age, but people of the same age in years may not be alike in terms of underlying health. Underlying health can be estimated with various “biomarkers.” Our proposal is designed to identify a new biomarker that shows whether a patient is fit for stem cell transplant. We are studying clonal hematopoiesis of indeterminate potential (CHIP), a group of genes that indicate the health of a patient’s blood cells. Our hypothesis is that patients with CHIP in the blood before stem cell transplant will have poor outcomes after transplant. To test this, we will use a large collection of blood samples taken from blood cancer patients before stem cell transplant. We also have information about each patient’s health after transplant. We will use DNA sequencing to measure CHIP genes in the blood samples. We will use statistics to compare CHIP in the samples with patient health after stem cell transplant. If these correlate, it will show that CHIP is a good biomarker for use in a risk-prediction model. This will help doctors make personalized decisions that improve the lives of blood cancer patients.
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