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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要大约 10,000 名患者接受同种异体造血细胞移植 (HCT) 每年在美国。移植相关血栓性微血管病（TA-TMA）是一种罕见但往往致命的血液并发症，表现为不受控制的微血管病变溶血性贫血（MAHA）、血小板减少、微血管血栓形成，严重时，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 的发生率和临床危险因素。建立在根据以往的经验，我们当前提案的目标是测试这些临床预测因素以及与 TA-TMA 开发相关的独立前瞻性实验室生物标志物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 的发病率和移植后早期危险因素结合临床信息学使用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，结合了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 奖申请人李安博士完全有资格开展该项目。他是致力于成为一名独立资助的、以患者为中心的良性医学科学家血液学。他提出了一个全面的五年职业发展计划来帮助他从监督研究向独立研究的转变。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（主要隶属关系）贝勒学院流行病学和人口科学系（二级附属机构）医学学院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。