The Association of Microbiota Composition With cGVHD After Allo-HSCT

Study Overview
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Brief Summary
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Previous studies had found that the microbe in intestinal after allogeneic hematopoietic cell transplantation(allo-HSCT) were closely associated with overall survival and post-transplantation complications, especially graft versus host disease (GVHD).Due to the limited data on the association of microbiota composition with chronic GVHD(cGVHD) after allogeneic hematopoietic stem cell transplantation, the relationship between microbiota composition and post-transplantation complications, especially cGVHD, needs to be further evaluated.Detailed studies of the microbiome and host immune system will lead to the discovery of microbiome markers for early identification of patients at high risk for cGVHD. This may regulate patients' gut microbiota in an individualized manner to achieve optimal treatment outcomes while avoiding severe post-transplant cGVHD. We will operate a prospective, multicenter, nonrandomized, observational study. Patients will be asked to provide blood and stool samples during allo-HSCT.

Detailed Description
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Previous studies had found that the microbe in intestinal after allogeneic hematopoietic cell transplantation(allo-HSCT) were closely associated with overall survival and post-transplantation complications, especially graft versus host disease (GVHD).Due to the limited data on the association of microbiota composition with chronic GVHD(cGVHD) after allogeneic hematopoietic stem cell transplantation, the relationship between microbiota composition and post-transplantation complications, especially cGVHD, needs to be further evaluated.Detailed studies of the microbiome and host immune system will lead to the discovery of microbiome markers for early identification of patients at high risk for cGVHD. This may regulate patients' gut microbiota in an individualized manner to achieve optimal treatment outcomes while avoiding severe post-transplant cGVHD. We will operate a prospective, multicenter, nonrandomized, observational study. Patients will be asked to provide blood and stool samples during allo-HSCT. This blood will be used for plasma banking for further analysis, including miR, chemokine and metabonomics detection. Stool will be used for microbiome studies - isolation of total DNA/RNA and 16S rRNA gene sequencing for bacterial taxonomic classification. Furthermore, metagenomic sequencing and subsequent taxonomic and functional classification of microbial genes will be used.

Official Title
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The Association of Microbiota Composition With Chronic Graft Versus Host Disease

Conditions
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Hematopoietic Stem Cell Transplantation, Hematologic Malignancy, Chronic Graft-versus-host-disease, Complication

Intervention / Treatment
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* Other: blood sample
* Other: stool sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged between 18 years and 65 years patients planned to be treated by allogeneic hematopoietic cell transplantation signed written informed consent Exclusion Criteria: patients not-matching inclusion criteria

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| observational group<br>Patients with hematologic malignancies following allogeneic hematopoietic stem cell transplantation treatment | Other: blood sample<br>* collecting 15ml peripheral blood samples at -7 days before transplantation and+28 days, +100 days, +1 years, +2 years after transplantation<br>Other: stool sample<br>* collecting 50mg fresh stool samples at -7 days before transplantation and+28 days, +100 days, +1 years, +2 years after transplantation<br>|
| control group<br>health control group: healthy volunteers | Other: blood sample<br>* collecting 15ml peripheral blood samples at -7 days before transplantation and+28 days, +100 days, +1 years, +2 years after transplantation<br>Other: stool sample<br>* collecting 50mg fresh stool samples at -7 days before transplantation and+28 days, +100 days, +1 years, +2 years after transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbial changes in stool as measured by 16S rRNA gene sequencing in hematological cancer patients before, at time and after hematopoietic cell transplantation | Microbial changes of stool will be assessed before, at time and after hematopoietic cell transplantation | 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To correlate microbial changes in stool as measured by 16S rRNA gene sequencing with the post-transplant complications in allogeneic transplant settings (cGVHD, overall survival, non-relapse mortality, replase, infectious complications) | To assess microbial changes with toxicity of therapy | 100 days | 
| To correlate microbial changes in stool as measured by 16S rRNA gene sequencing with the patients reported outcomes | To correlate microbial changes with the quality of life which measured by Short Form 36 (SF-36) and and Functional Assessment of Chronic Illness Therapy with BMT subscale (FACT-BMT) | 100 days | 
| To correlate microbial changes in stool as measured by 16S rRNA gene sequencing with the patients nutrition status | To correlate microbial changes with the patients nutrition. Clinical and biological nutritional assessments included anthropometric measurements, serum nutritional proteins, body composition assessed by bioelectrical impedance, and upper-limb muscle strength (MS) measured by dynamometry. | 100 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hematopoietic stem cell transplantation, microbiota, metabolomics, chronic graft versus host disease