Assessment of Clonal Hematopoiesis and Its Relationship to Cardiovascular Disease in Hodgkin Lymphoma Survivors
Abstract
Lay Abstract: This clinical research project is designed to improve our understanding of how cancer therapy for pediatric and adolescent Hodgkin’s lymphoma (Topic Area) patients develop heart disease after receiving chemotherapy. We hope this effort will be a major advance in cancer survivorship (Focus Area) and lead to further studies to improve the lives of childhood cancer survivors who are cured of their disease. We have access to a large number of pediatric and adolescent Hodgkin’s lymphoma patients who were all treated on the same clinical trial and thus received very similar levels of therapy that are known to have toxic effects on the heart. We will use blood samples that were collected before therapy was started, after therapy was completed, and on two additional time points to see if we can identify cells in these samples that are called therapy-related clonal hematopoiesis. These cells have been shown to be associated with the development of heart disease following chemotherapy administration in animal model experiments performed by our research team. We wish to see whether, in fact, this observation occurs in pediatric and adolescent lymphoma survivors. We will look to see if these cells emerge and expand in numbers in the study subjects, and we will use cardiac magnetic resonance imaging, which we and others have shown to be useful in detecting heart abnormalities earlier than other testing tools. We hypothesize that therapy-related clonal hematopoiesis develops as a consequence of cancer therapy, and their expansion will be associated with heart damage demonstrated by cardiac magnetic resonance imaging. We will also examine whether patients who possess traditional risk factors for heart disease (overweight, high cholesterol, high blood pressure, etc.) are at even greater risk for showing abnormalities of the heart. We expect to validate our hypothesis within the 4-year funding period of this trial, which will be a significant patient-related outcome. Success in this project will overcome the Fiscal Year 2021 Peer Reviewed Cancer Research Program Overarching Challenge of developing strategies to improve ease of care/accessibility and to address survivorship issues. If we demonstrate that therapy-related clonal hematopoiesis is linked to heart disease, measuring these cells in pediatric and adolescent lymphoma survivors can be used to identify patients at risk for heart disease earlier than what is currently practiced, to provide treatments before severe heart disease develops. Furthermore, if conventional risk factors for heart disease (overweight, high cholesterol, high blood pressure, etc.) are shown to make the situation worse, we can refer patients to medical providers who could prescribe interventions to improve these risk factors and further reduce the risk of permanent heart disease. Finally, support of the role of therapy-related clonal hematopoiesis in the development of heart disease will lead to further investigations on how these cells lead to heart damage. Such work will hopefully lead to treatments directed toward these cells that may further reduce the survivors’ risk for heart disease and early loss of life from this complication. Success in this effort would be a major advance in cancer survivorship. This work could substantially impact active-duty Service Members, Veterans, and other military beneficiaries. Improving our understanding on how cancer therapy impacts the heart and providing strategies to maintain the health of a pediatric and adolescent lymphoma patient can ease a parent or guardian’s concerns, providing them with a more positive outlook and maintaining their mission readiness. Maintaining the pediatric and adolescent lymphoma patient’s cardiac health will reduce the likelihood of the need for more extensive medical interventions and hospitalizations that would incur if the pediatric and adolescent lymphoma survivor’s heart would deteriorate.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210667
Entities
People
- Kenneth Walsh
Organizations
- United States Army
- University of Virginia