Clinical trial NCT06102694: Identification of Plasma Biomarkers for Early Diagnosis of Transplant-associated Thrombotic Microangiopathy
Official title: Screening and Identification of Plasma Biomarkers for Early Diagnosis of Transplant-associated Thrombotic Microangiopathy Based on Proteomics and Metabolomics Techniques
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Thrombotic Microangiopathies
Hematopoietic Stem Cell Transplantation
Keywords: TA-TMA
Hematopoietic Stem Cell Transplantation
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2023-10-26
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will include patients aged 18 years and older who have undergone allogeneic hematopoietic stem cell transplantation for hematologic disorders. Complement, blood smear, renal function, and complete blood count tests at specified time points will be conducted to assess the patients' health status. The investigators anticipate enrolling a minimum of 300 patients and will calculate the incidence rate of TA-TMA according to international diagnostic standards.Based on subsequent occurrences of TATMA in patients, the study population will be categorized into two groups: the TATMA occurrence group and the non-TATMA occurrence group.The objective of this study is to gain insights into the potential role of complement testing in TA-TMA

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.

Eligibility criteria: 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

Primary outcomes:
measure: The frequency of TA-TMA
timeFrame: 100 days after transplantation
measure: Risk factors for TA-TMA
timeFrame: one year after transplantation
measure: levels of sC5b-9 at regular times
timeFrame: before transplantation, 0 days, 14 days, 28 days, 42 days and 60days after transplantation
Secondary outcomes:
measure: overall survival
timeFrame: one or two years after transplantation
measure: non-relapse mortality
timeFrame: one or two years after transplantation
measure: acute graft versus host disease
timeFrame: three months after transplantation
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
Study officials:
affiliation: Chinese Academy of Medical Sciences
name: Erlie Jiang
role: PRINCIPAL_INVESTIGATOR
References: