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

移植相关血栓性微血管病 (TA-TMA) 的流行病学和生物标志物：前瞻性验证队列研究

• 批准号: 10597124
• 负责人: Ang Li
• 金额: $ 17.47万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10597124
• 关键词: Acute Graft Versus Host Disease; Address; Adult; Advisory Committees; Age; Allogenic; Alveolar; Angiopoietin-2; Aspergillosis; Benign; Bioethics; Biological Markers; Biological Specimen Banks; Biometry; Blood Vessels; Calcineurin inhibitor; Child; Childhood; Chronic Kidney Failure; Clinical; Clinical Data; Clinical Informatics; Cohort Studies; Complement; Complement Activation; Complication; Data; Development; Development Plans; Diagnosis; Diffuse; Disease; Dose; Early Diagnosis; End stage renal failure; Endothelium; Enrollment; Environment; Enzyme-Linked Immunosorbent Assay; Epidemiologic Factors; Epidemiology; Funding; Future; Grant; Hematological Disease; Hematology; Hemolytic Anemia; Hemorrhage; Immune; Immunoassay; Incidence; Infection; Informatics; Injury; Institution; Intervention Trial; Judgment; Kidney; Laboratories; Measures; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentorship; Modeling; Monitor; Morbidity - disease rate; Nested Case-Control Study; Neurologic Dysfunctions; Organ; Outcome; Outcomes Research; Pathogenesis; Pathway interactions; Patient-Focused Outcomes; Patients; Pediatric Hospitals; Pediatric cohort; Pharmaceutical Preparations; Physicians; Population Sciences; Prospective cohort; Prospective, cohort study; Qualifying; Rare Diseases; Regimen; Reporting; Research; Research Training; Retrospective Studies; Retrospective cohort study; Risk; Risk Factors; Risk Marker; Scientist; Sirolimus; Source; Southwestern United States; Steroids; Testing; Texas; Thrombocytopenia; Thrombosis; Time; Toxic effect; Training; Transplant Recipients; Transplantation; United States; Validation; Viremia; adjudication; career development; clinical diagnosis; clinical diagnostics; clinical epidemiology; clinical predictors; clinical risk; college; complement pathway; design; diagnostic criteria; early detection biomarkers; effective therapy; experience; follow-up; genetic association; graft vs host disease; hematopoietic cell transplantation; improved; kidney dysfunction; lateral flow assay; mortality; novel; patient oriented; pediatric patients; post-transplant; predictive tools; prospective; risk prediction; risk stratification; screening; specific biomarkers; success; thrombotic; transplant centers

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.

项目摘要/摘要 大约10,000例患者接受同种异体造血细胞移植（HCT） 每年在美国。移植相关的血栓形成微动病（TA-TMA）是一个 罕见但通常是致命的血液学并发症，表现出不受控制的微动性 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， 永久神经系统或肾功能障碍。我们最近完成了一个大型回顾群体 研究阐明TA-TMA的发生率和临床风险因素的研究。建立在 以前的经验，我们当前建议中的目标是测试这些临床预测指标 和与TA-TMA开发相关的实验室生物标志物在独立的前景中 儿科队列以改善早期检测和风险分层。我们提出以下目标： 目标1：确定ta-tma的发病率和早期移植后风险因素 纳入临床信息学使用的前瞻性小儿队列研究。目标2：测试 TA-TMA的动态风险预测工具，该工具包含经过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Ang Li博士的资格良好，可以进行拟议项目。他是 致力于成为良性的独立资助的由患者的独立医师科学家 血液学。他提出了一项全面的五年职业发展计划，以帮助他 从监督研究过渡到独立性。具体来说，他设想了一个强大的 指导小组，正式咨询委员会，一个现实的流行病学课程培训， 生物统计学，临床信息学和生物伦理学。血液学部分（主要隶属关系） 贝勒学院的流行病学和人口科学（次级隶属关系）的部分 医学提供理想的研究培训环境，该机构完全致力于 他的职业发展。