Dysbiosis and Immune Reconstitution After Allo-HSCT

Study Overview
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Brief Summary
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Preliminary (proof of concept), monocentric, interventional, prospective, non-randomized and analytic trial designed to simultaneously explore intestinal microbiota changes and early post-transplant immune reconstitution, and to correlate biological data with clinical data (antibiotics use, stress level, GVHD).

Detailed Description
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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the major curative therapeutic approach for hematologic neoplasms. After HSCT, patients have a compromised GI mucosal barrier and an altered microbiota, also called dysbiosis. The later could be due to conditioning or use of broad-spectrum antibiotics, and could be accentuate by stress encountered by patients during their therapy management. Recent data have shown that alterations in the intestinal flora are associated with bad outcome, particularly with graft-versus-host disease (GVHD), bacteremia, and reduced overall survival post-transplantation. How intestinal bacteria can modulate the risk of relapse after HSCT is yet unknown. The scientists hypothesize that the variation of some bacterial taxa may influence post-transplant immune reconstitution, particularly invariant Natural Killer T cells.

Official Title
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Intestinal Dysbiosis and Immune Reconstitution After Allogeneic Hematopoietic Cell Transplantation

Conditions
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Hematopoietic Stem Cell Transplantation

Intervention / Treatment
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* Biological: blood samples
* Biological: fecal samples
* Behavioral: Anxiety test
* Behavioral: Stress test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients > 18 years affiliated to a social security system Patients followed at the hospital of Nancy for a allogeneic hematopoietic cell transplantation (HLA matched donor) Graft of peripheral blood stem cell GVHD prophylaxis by ciclosporin and antilymphocyte serum +/- mycophenolate mofetil or methotrexate. Exclusion Criteria: HIV+ patients Patients with active HBV or HCV

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patient<br>For all patients included in the study, the following interventions will be performed : several blood samples (quantity collected requiring classification of this study as interventional according to French law) several fecal samples anxiety tests stress tests | Biological: blood samples<br>* 20 to 30 ml of blood sample (D0, D15, D30, D60, D90, D180, Y1, Y2)<br>Biological: fecal samples<br>* 1 g of feces (D-8, D0, D15, D30, D90)<br>Behavioral: Anxiety test<br>* Test of Spielberger<br>Behavioral: Stress test<br>* Test of Cohen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of iNKT reconstitution after HSCT (good/poor) |  | Day 90, | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gut microbiota composition | relative abundance of intestinal bacterial taxa | Day 0, Day 15, Day 30, Day 90 | 
| immune reconstitution after HSCT (other immune cells) | quantification of Tregs, MDSC, MAIT, T lymphocytes | Day 15, Day 30, Day 60, Day 90, Day 180, Year 1, Year 2 | 
| GVH disease | yes/not | Day 30, Day 60, Day 90 | 
| use of antibiotics | yes/not (molecules, delay, posology) | Day 0, Day 15, Day 30, Day 60, Day 90 | 
| level of stress | test of Cohen | Day -8, Day 15, Day 30, Day 90 | 
| level of anxiety | test of Spielberger | Day -8, Day 15, Day 30, Day 90 | 
| quality of iNKT reconstitution after HSCT (good/poor) |  | Day 15, Day 30, Day 60, Day 180, Year 1, Year2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HSCT, intestinal dysbiosis, immune reconstitution