Mentor Name: Oriana Miltiadous

The gut microbiome plays a critical role in modulating the immune response, influencing outcomes of allogeneic transplantation, a life-saving treatment for relapsed/refractory leukemia and lymphoma. However, this treatment comes with significant complications that can limit its efficacy. Understanding and leveraging the immunomodulatory potential of the microbiome is crucial for optimizing cancer therapy outcomes. However, the mechanisms underlying the microbiome's influence on outcomes post-transplant, especially in pediatric patients, remain insufficiently understood. Early recovery of key immune cells post-transplant is a predictor of superior overall survival and low risk of graft versus host disease and mortality. Microbiota and microbe-derived bile acids have been identified as regulators of the immune system, suggesting a mechanism through which the microbiome affects hematopoietic transplant outcomes. The proposed project aims to unravel the intricate relationship between the microbiome, bile acids, and allogeneic hematopoietic transplantation outcomes in pediatric recipients. My long-term goal is to identify therapeutic interventions that optimize the microbiota composition, facilitating superior immune function and improve treatment tolerance for enhanced clinical outcomes. The project will leverage a substantial sample size from three large centers (411 patients), ensuring statistical and clinical significance.