Chemotherapy and radiation therapy are used to successfully treat many types of cancer. However, these treatments also damage healthy blood and bone marrow cells, increasing the risk for effects including low blood counts and blood cancers such as therapy- related myelodysplastic syndrome (tr-MDS). Tr-MDS limits the ability to safely continue primary cancer treatment. Additionally, tr- MDS is often resistant to available chemotherapy treatments and is associated with a life expectancy of less than 1 year following diagnosis. Strategies to predict and reduce the risk of tr-MDS would significantly reduce cancer-related death. Many patients with cancer have clonal hematopoiesis (CH), a precursor of blood cancers such as MDS. We previously developed the CH risk score (CHRS), a risk prediction tool that helps clinicians estimate the likelihood of progression from CH to MDS. However, the CHRS is not validated in patients receiving cancer treatment. The clonal hematopoiesis chemotherapy and radiation effects (CH CARE) study will prospectively monitor cancer patients to understand the evolution and consequences of CH. In aim 1, we examine the influence of CH on the development of clinically significant low blood counts during cancer treatment. Aim 2 identifies factors impacting growth of cells with CH during cancer therapy. Then, aim 3 identifies features associated with an increased risk of tr-MDS resulting in a dedicated clinical algorithm to predict tr-MDS risk in cancer patients.