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

项目总结/摘要 大约10，000名患者接受异基因造血细胞移植（HCT） 每年在美国。移植相关血栓性微血管病（TA-TMA）是一种 一种罕见但通常致命的血液学并发症，表现为不受控制的微血管病变 溶血性贫血（MAHA）、血小板减少症、微血管血栓形成，在严重的情况下， 永久性神经或肾功能障碍。我们最近完成了一项大型回顾性队列研究， 研究旨在阐明TA-TMA的发病率和临床风险因素。的基础上继续努力 根据以往的经验，我们在当前提案中的目标是测试这些临床预测因子 在一项独立的前瞻性研究中， 儿科队列，以改善早期发现和风险分层。我们提出以下目标： 目的1：确定TA-TMA的发生率和移植后早期风险因素， 采用临床信息学的前瞻性儿科队列研究。目标2：测试 TA-TMA的动态风险预测工具，包括经验证的临床和实验室 免疫、内皮和补体激活途径中的生物标志物。 K23奖申请人李昂博士完全有资格进行拟议的项目。他是 致力于成为一个独立资助的以病人为导向的医生科学家在良性 血液学他提出了一个全面的五年职业发展计划， 从监督研究到独立研究。具体来说，他设想了一个强大的 指导小组，正式的咨询委员会，流行病学的现实课程培训， 生物统计学、临床信息学和生物伦理学。血液科（主要附属机构） 贝勒学院流行病学和人口科学科（二级附属机构） 提供理想的研究培训环境，并致力于 他的职业发展。

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.