Alterations in Intestinal Microbiota, Metabolites, and Immune Cells in Allo-HSCT

Alterations in Intestinal Microbiota, Metabolites, and Immune Cells Pre- and Post-Transplantation of Allogeneic Hematopoietic Stem Cells

This research project delves into the critical role of gut immunity in the occurrence and progression of acute graft-versus-host disease (aGVHD) post allogeneic hematopoietic stem cell transplantation (allo-HSCT). Addressing the current gaps in understanding the involvement of intestinal microbiota, metabolites, and cellular metabolism in clinical aGVHD, the study involves comprehensive analyses on 200 allo-HSCT patients and 50 healthy volunteers. By scrutinizing changes in gut microbiota, metabolites, and immune cell metabolism, the research aims to shed light on their roles in allo-HSCT and their correlation with post-transplant complications. The findings are poised to offer crucial insights for diagnosing and prognosticating complications following transplantation.

Study Overview

• Status: Recruiting
• Conditions: Graft Vs Host Disease
• Intervention / Treatment: Diagnostic test: Blood Sample; Diagnostic test: Stool Sample; Diagnostic test: Urine Sample

Detailed Description

The intestinal immune system plays a pivotal role in the onset, progression, and evolution of acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the precise contributions and mechanisms underlying the involvement of intestinal microbiota, metabolites, and cellular metabolism in immune regulation during clinical aGVHD remain unclear.

This research initiative aims to collect peripheral blood, fecal, and urine samples from 200 patients before and after transplantation as well as 50 healthy volunteers. Comprehensive analyses, including metagenomics, 16S rRNA sequencing, transcriptomics, metabolomics, single-cell sequencing, as well as assessments of immune cell function and inflammatory cytokines, will be conducted. Additionally, longitudinal follow-up observations will be performed to monitor post-transplant complications, relapse and immune reconstitution.

By investigating the dynamics of gut microbiota, metabolites, and cellular metabolism and analyzing their correlation with changes in immune responses, this study seeks to elucidate the roles of intestinal microbiota, metabolites, and immune cell metabolism in the context of allo-HSCT. The findings are anticipated to provide insights into the correlation between these factors and outcomes of allo-HSCT patients, contributing valuable evidence for the diagnosis and prognosis assessment of complications following transplantation.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Yang Xu, M.D; Phone Number: +86 521 67780322; Email: yangxu@suda.edu.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Yang Xu, M.D; Phone Number: +86 521 67780322; Email: yangxu@suda.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Hematological patients will receive allo-HSCT in short time.

Description

Inclusion Criteria:

• Patients with hematologic disorders undergoing allo-HSCT.

Exclusion Criteria:

• Patients with confirmed pathogenic intestinal infections and severe systemic infections at the time of sampling.
• Diagnosis of autoimmune diseases, metabolic disorders, and chronic gastrointestinal diseases.
• Pre-transplant diseases not in complete remission.
• Post-transplant hematopoietic engraftment failure or pre-engraftment mortality.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Volunteers	Diagnostic test: Blood Sample; 6 ml blood (collection occurs once pre-transplantation and at three designated follow-up time points post-transplantation); Diagnostic test: Stool Sample; pea-sized amount (collection occurs once pre-transplantation and at three designated follow-up time points post-transplantation); Diagnostic test: Urine Sample; 8 ml (collection occurs once pre-transplantation and at three designated follow-up time points post-transplantation)
Allo-HSCT Recipients	Diagnostic test: Blood Sample; 6 ml blood (collection occurs once pre-transplantation and at three designated follow-up time points post-transplantation); Diagnostic test: Stool Sample; pea-sized amount (collection occurs once pre-transplantation and at three designated follow-up time points post-transplantation); Diagnostic test: Urine Sample; 8 ml (collection occurs once pre-transplantation and at three designated follow-up time points post-transplantation)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Complications	Recording and monitoring the occurrence of complications such as infection, GVHD, etc., documenting their onset time, type, severity, and management.	2 years
Relapse	Documenting and monitoring the occurrence of relapse in study subjects, including recording the time of onset, severity, and management.	2 years
Overall Survival	OS will be assessed from the first day of stem cells infused to death or last follow-up.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Function	Incidence of neutrophil recovery; Incidence of lymphocyte and monocyte subset recovery	Measured 3 months after stem cells infused

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Study Chair: Yang Xu, M.D, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: November 16, 2023
• First Submitted That Met QC Criteria: November 16, 2023
• First Posted (Actual): November 22, 2023

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Immunity; Metabolites; Intestinal Microbiota; Allo-HSCT
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: Pre-Post Allo-HSCT Monitoring

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No