Faecal Microbiota Transplantation After Allogeneic Stem Cell Transplantation

GRFS is a composite endpoint of GvHD-free/relapse-free survival in which events include grade II-IV acute GvHD, moderate and severe chronic GvHD, relapse, or death in the first year post-HSCT. GRFS will be measured at one year after allo-HSCT and compared between both groups of patients.

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

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.

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

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

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.

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.

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

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.

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.

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.

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.

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.

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

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

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).

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.

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).

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.

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.

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.