Epidemiology and Biomarkers in Transplant Associated Thrombotic Microangiopathy (TA-TMA): A Prospective Validation Cohort Study

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Project Summary/Abstract Approximately 10,000 patients receive an allogeneic hematopoietic cell transplantation (HCT) annually in the United States. Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare but often fatal hematologic complication that manifests with uncontrolled microangiopathic hemolytic anemia (MAHA), thrombocytopenia, microvascular thrombosis, and in severe cases, permanent neurologic or kidney dysfunction. We recently completed a large retrospective cohort study to elucidate the incidence of and clinical risk factors for TA-TMA. Building upon the previous experience, our objectives in the current proposal are to test these clinical predictors and laboratory biomarkers associated with TA-TMA development in an independent prospective pediatric cohort to improve early detection and risk stratification. We propose the following aims: Aim 1: To determine the incidence and early post-transplant risk factors for TA-TMA in a prospective pediatric cohort study that incorporates the use of clinical informatics. Aim 2: To test a dynamic risk prediction tool for TA-TMA that incorporates validated clinical and laboratory biomarkers in immune, endothelial, and complement activation pathways. The K23 award applicant, Dr. Ang Li, is well-qualified to conduct the proposed project. He is committed to becoming an independently funded patient-oriented physician scientist in benign hematology. He has proposed a comprehensive five-year career development plan to help his transition from supervised research to independence. Specifically, he envisions a strong mentorship panel, a formal advisory committee, a realistic coursework training in epidemiology, biostatistics, clinical informatics, and bioethics. The Section of Hematology (primary affiliation) and Section of Epidemiology and Population Sciences (secondary affiliation) at Baylor College of Medicine offer an ideal research training environment and the Institution is fully committed to his career development.