Identification of Plasma Biomarkers for Early Diagnosis of Transplant-associated Thrombotic Microangiopathy
Study Details
Study Description
Brief Summary
The goal of this clinical trial is to learn about plasma biomarkers of diagnosed transplant-associated thrombotic microangiopathy (TA-TMA) in patients undergoing transplantation. The main questions it aims to answer are: whether there are molecules that can accurately diagnose and predict TA-TMA; whether the current biomarkers related to TA-TMA can well predict the occurrence and survival of TA-TMA in adult patients with malignant hematopoietic diseases, for example, acute leukemia. Participants will receive laboratory tests of peripheral blood and urine specimens related to TA-TMA at regular times after transplantation.
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Detailed Description
Transplant-associated thrombotic microangiopathy (TA-TMA) is a commonly serious complication after hematopoietic stem cell transplantation (HSCT). As the diagnostic criteria are not standardized, the incidence of TA-TMA has been reported in the literature to be 0.5%-64%. TA-TMA has an insidious onset, diverse clinical manifestations, rapid progression, limited therapeutic options, and a poor prognosis, with a mortality rate of 60%-90%. The exact pathogenesis of TA-TMA is not yet fully understood. Markers of endothelial damage such as thrombomodulin (TM), plasminogen activator inhibitor-1(PAI-1), intercellular adhesion molecule-1(ICAM-1), and soluble membrane attack complex (sC5b-9) may have predictive roles, but there is a lack of large-scale prospective clinical studies to confirm it. The emergence of multi-omics technologies has brought biomarker research into the high-throughput stage. However, proteomics and metabolomics biomarkers have not been reported in TA-TMA research. In this study, we will establish the first prospective study cohort for screening early warning biomarkers of TA-TMA in China, collect transplantation-related clinical data, and collect plasma serial samples from post-transplantation patients, which are expected to obtain new biomarkers that can be used in the early diagnosis of TA-TMA through the combined analysis of proteomics and metabolomics.
The contents of this study are as follows:
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Establish the first prospective study cohort for screening TA-TMA early warning biomarkers in China. Patients will be enrolled continuously who undergo HSCT in order to build a prospective study cohort to search for clinical phenotypes related to the occurrence, evolution, or prognosis of TA-TMA, and to excavate the risk factors of TA-TMA, prognostic factors, etc. Collect complete transplantation-related clinical data, and plasma serial samples at fixed testing time points. SC5b-9, urine protein to creatinine ratio, lactate dehydrogenase, blood rountine, schistocytes will be detected at regular times.
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According to the diagnostic criteria of TA-TMA, TA-TMA patients and 1:1 matched non-TA-TMA patients will be screened, and the training set (30 cases each) and validation set (10 cases each) will be established respectively. Plasma warning biomarkers with high sensitivity, stability, and accuracy will be screened and identified from the large amount of data by proteomics and metabolomics technologies.
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We intend to utilize the opportunity of this clinical study to collect clinical data and biological samples from HSCT patients, establish a clinical database and biological samples bank for TA-TMA disease, and provide sample support for subsequent translational research.
Study Design
Outcome Measures
Primary Outcome Measures
- The frequence of TA-TMA [100 days after transplantation]
diagnostic criteria is based on Jodele's criteria
- Risk factors for TA-TMA [one year after transplantation]
Find risk factors for patients with TA-TMA
- levels of sC5b-9 at regular times [before transplantation, 0 days, 14 days, 28 days, 42 days and 60days after transplantation]
to detect the levels of sC5b-9 at regular times after transplantation
Secondary Outcome Measures
- overall survival [one or two years after transplantation]
the overall survival for patients
- non-relapse mortality [one or two years after transplantation]
the non-relapse mortality for patients
- acute graft versus host disease [three months after transplantation]
report the rate of acute graft versus host disease
Eligibility Criteria
Criteria
Inclusion Criteria:
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- Age 18-60 years, regardless of sex 2. HSCT patients without progression or recurrence
Exclusion Criteria:
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- Patients with persistent or active infections including bacterial, fungal and viral infections 2.Patients with severe organ dysfunction 3.Patients unable to comply with the study protocol due to other circumstances
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Institute of Hematology & Blood Diseases Hospital, China
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TMA-20230910