Faecal Microbiota Transplantation After Allogeneic Stem Cell Transplantation

Overall survival

Overall survival is defined as the time period between the date of randomization and the date of death, regardless of its cause.

Time frame: At Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantation

Progression-free survival

Progression-free survival is defined as the time period between the date of randomization and the date of disease relapse or progression or death, regardless of its cause.

Time frame: At Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantation

Haematopoietic reconstitution

Haematopoietic reconstitution is assessed by: 1/ turnaround time of polynuclear neutrophils \>0.5.10\^9/L (first day within a period of three consecutive days); 2/ spontaneous platelet turnaround time \>20.10\^9/L (two days with no platelet transfusion within the previous three days); 3/ spontaneous platelet turnaround time \>50.10\^9/L (two days with no platelet transfusion within the previous three days); 4/ the number of transfusions of red blood cells and platelets between D0 and D100

Time frame: At the time of haematopoietic reconstitution

Engraftment rates

Engraftment rates are evaluated by a chimerism measure (by molecular biology)

Time frame: At Day 30, Day 60, Day 90, Day 180, Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantationday

Cumulative incidence of acute GvHD

Acute GvHD severity is defined according to MAGIC criteria. It will be notified by specifying the location (liver, skin, gut …), the severity score (II to IV), the treatment applied and the efficacy of treatment. GvHD occurrence will be notified every week until D30 (minimum) or until hospital discharge, then monthly until D180 and at D270, D360, D540 and D720.

Time frame: At Day 360 after allogeneic hematopoietic stem cell transplantation

Cumulative incidence of chronic GvHD

Chronic GvHD severity will be defined according to NIHCC criteria. It will be notified by specifying the location (liver, skin, gut …), the severity score (II to IV), the treatment applied and the efficacy of treatment. GvHD occurrence will be notified every week until ungraftment, then monthly until D180 and at D270, D360, D540 and D720.

Time frame: At Day 720 after allogeneic hematopoietic stem cell transplantation

Transplant-Related Mortality

Transplant-related mortality is defined as death due to causes unrelated to the underlying disease.

Time frame: At Day 180, Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantation

Cumulative incidence of infections

Infectious complications will be notified every week up to day 30 (minimum) or until hospital discharge, then every month up to D180 and from D270 to D360, according to the existence of a documented bacteraemia, germ resistance, type and number of days of curative antibiotherapy used; the existence of a documented fungal infection and the type and number of days of curative antifungal treatment; the existence of a documented viral infection and the type and number of days of curative antiviral treatment; the need of an intensive care unit transfer due to an infectious complication.

Time frame: At Day 360 after allogeneic hematopoietic stem cell transplantation

Severe infections description

Severe infections will be defined according to GREFIG score : bactearemia with severe sepsis, complex bactearemia (with deep organ involvement), candidemia (at least one positive blood culture) with sepsis or deep infected site, proven or probable aspergillosis pneumonia, severe varicella-zoster virus infection (involvement of a deep organ or associated coagulopathy), any viral encephalitis, CMV infection with lung or digestive location, Pneumocystis jiroveci pneumonia, toxoplasmosis with involvement of organ or central nervous system, any acute pneumonia with PaO2 less than or equal to 65mmHg, any sepsis requiring transfer to an intensive care unit.

Time frame: From the day of inclusion to Day 360 after allogeneic hematopoietic stem cell transplantation

Impact of Fecal Microbiota Transplantation (FMT) on multi-resistant bacteria, extended-spectrum beta-lactamases and Clostridium difficile infection

Impact of FMT on multi-resistant bacteria, extended-spectrum beta-lactamases and Clostridium difficile infection will be assessed by evaluation of persistence or disappearance of these pathogenic bacteria after FMT.

Time frame: At Day 360 after allogeneic hematopoietic stem cell transplantation

Unexpected event description that could be in relation with FMT of Fecal Microbiota Transplantation (FMT)

Each unexpected event that could be in relation with FMT will be notified: abdominal pain, diarrhea, bacterial translocation or any adverse effect attributed to the enema.

Time frame: From the day of FMT to Day 360 after allogeneic hematopoietic stem cell transplantation

Quality of life assessment

The quality of life will be auto-evaluated by the patients using a validated questionnaire: European Organisation for Research and Treatment of Cancer- Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Time frame: at Day -7, Day 30, Day 90, Day 180, Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantation

Analysis the intestinal microbiota in patients

The intestinal microbiota composition and diversity will be assessed by 16S-rRNA sequencing performed prospectively in all patients with FMT and without FMT.

Time frame: Before the conditioning regimen, before the FMT and at Day 30, Day 90 and Day 360 after white blood cells recovery

Analysis the intestinal microbiota in stool donnors

The intestinal microbiota composition and diversity will be assessed by 16S-rRNA sequencing performed prospectively in all stool donnors.

Time frame: At the time of the first stool donnation between Day 7 to Day 55 after the inclusion

Blood collection for a metabolomic study in patients

A blood collection will be set up from blood samples collected on patients from both groups. These samples will be used for a metabolomic study (tryptophan, indoleamine 2,3-dioxygenase, short chain fatty acid, bile acids).

Time frame: Before the conditioning regimen, before the FMT and at Day 30, Day 90 and Day 360 after white blood cells recovery

Blood collection for an analysis of anti-microbiota IgG and IgA in patients

A blood collection will be set up from blood samples collected on patients from both groups. These samples will be used for an analysis of anti-microbiota IgG and IgA.

Time frame: Before the conditioning regimen, before the FMT and at Day 30, Day 90 and Day 360 after white blood cells recovery

Blood collection for a metabolomic study in stool donnors

A blood collection will be set up from blood samples collected on stool donnors. These samples will be used for a metabolomic study (tryptophan, indoleamine 2,3-dioxygenase, short chain fatty acid, bile acids).

Time frame: At the time of the first stool donnation between Day 7 to Day 55 after the inclusion

Blood collection for an analysis of anti-microbiota IgG and IgA in stool donnors

A blood collection will be set up from blood samples collected on stool donnors. These samples will be used for an analysis of anti-microbiota IgG and IgA.

Time frame: At the time of the first stool donnation between Day 7 to Day 55 after the inclusion

Stool collection for an analysis of the virome in patients

A stool collection will be carried out from stool samples collected on patients from both groups.These samples will be used for an analysis of the virome evolution.

Time frame: Before the conditioning regimen, before the FMT and at Day 30, Day 90 and Day 360 after white blood cells recovery

Stool collection for an analysis of the virome in stool donnors

A stool collection will be carried out from stool samples collected on stool donnors.These samples will be used for an analysis of the virome evolution.

Time frame: At the time of the first stool donnation between Day 7 to Day 55 after the inclusion