Identification of Plasma Biomarkers for Early Diagnosis of Transplant-associated Thrombotic Microangiopathy

Recruiting

• Conditions: Thrombotic Microangiopathies; Hematopoietic Stem Cell Transplantation

• Registration Number: NCT06102694
• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital, China

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.

Detailed Description

Transplant-associated thrombotic microangiopathy (TA-TMA) is a commonly serious complication after allogeneic hematopoietic stem cell transplantation (allo-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, the investigors 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:

1. Establish the first prospective study cohort for screening TA-TMA early warning biomarkers in China. Patients will be enrolled continuously who undergo allo-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 routine, schistocytes will be detected at regular times.

2. 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.

3. intending to utilize the opportunity of this clinical study to collect clinical data and biological samples from allo-HSCT patients, establish a clinical database and biological samples bank for TA-TMA disease, and provide sample support for subsequent translational research.

Study Timeline

• Study First Submitted: 2023-10-22
• Study First Submitted QC: 2023-10-22
• Study First Posted: 2023-10-26
• Study Start: 2023-11-16
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-05
• Last Update Posted: 2023-12-06
• Primary Completion: 2025-01
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• 1. Diagnosis of a hematologic disease (e.g., leukemia, myelodysplastic syndromes,lymphoma) confirmed by histology or other appropriate diagnostic methods.
• 2. undergoing allo-HSCT
• 3. Age 18 years or older
• 4.Informed consent must be signed before the start of the study. For participants aged 18 and above, the informed consent should be signed by the patient or their immediate family member. Considering the patient's condition, if it is not favorable for the patient to sign, the informed consent may be signed by a legal guardian or immediate family member of the patient.

Exclusion Criteria

• 1. History of prior allogeneic hematopoietic stem cell transplantation
• 2. Persistent or active infections including bacterial, fungal and viral infections
• 3. Severe organ dysfunction
• 4. unable to comply with the study protocol due to other circumstances

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Risk factors for TA-TMA	one year after transplantation	Find risk factors for patients with TA-TMA
The frequency of TA-TMA	100 days after transplantation	diagnostic criteria is based on criteria proposed by Sonata Jodele
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

Name	Time	Method
non-relapse mortality	one or two years after transplantation	the non-relapse mortality for patients
overall survival	one or two years after transplantation	the overall survival for patients
acute graft versus host disease	three months after transplantation	report the rate of acute graft versus host disease

Trial Locations

Locations (1)

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences; 🇨🇳 Tianjin, China