This randomized, placebo-controlled phase IIb study (PHOEBUS trial) aims to evaluate the activity of fecal microbiotherapy MaaT033 to improve survival through the prevention of transplant-related complications in eligible alloHCT patients

Inclusion Criteria:

• Age ≥ 50 years old
• Presence of a hematologic malignancy for which an alloHCT is indicated with a reduced toxicity or reduced intensity conditioning regimen
• Patients with polynuclear neutrophils > 0.5 G/L
• Patients having received wide spectrum antibiotics within the last 90 days prior to inclusion
• Karnofsky index ≥ 70%
• Availability of a sibling donor, an unrelated stem-cell donor or a familial haploidentical donor
• Written informed consent

Exclusion Criteria:

• Patients planned to receive a non-myeloablative conditioning regimen (2 Gray total body irradiation (TBI) +/- purine analog, fludarabine + cyclophosphamide or equivalent)
• Patients planned to receive a conventional myeloablative conditioning regimen (e.g. high dose cyclophosphamide and high dose TBI (≥10Gy); high dose busulfan (12.8 mg/kg IV) + high dose cyclophosphamide)
• Patients receiving a manipulated graft (in-vitro T-cell depletion)
• Patients planned to receive a conditioning regimen with alemtuzumab
• Patients planned to receive alloHCT with cord blood cells
• Patients planned to receive alloHCT from unrelated donor with >= 3/10 HLA-mismatches
• Patients receiving a large spectrum antibiotic at time of randomization
• Patients planned to receive vedolizumab or abatacept for GvHD prophylaxis
• Creatinine clearance <30 mL/min
• Bilirubin or amino-transferases abnormalities contra-indicating alloHCT
• Cardiac ejection fraction less than 40%
• Pulmonary impairment with <50% lung carbon monoxide diffusing capacity (DLCO)
• Pregnancy
• Confirmed or suspected intestinal ischemia
• Confirmed or suspected toxic megacolon or gastrointestinal perforation
• Any history of gastro-intestinal surgery in the past 3 months
• Any history of chronic digestive disease (Crohn's disease, ulcerative colitis, inflammatory bowel disease or other relevant digestive condition according to physician's judgement)
• Known allergy or intolerance to trehalose or maltodextrin
• Patients with EBV-IgG negative serology
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
• Vulnerable patients such as: persons deprived of liberty, persons in Intensive Care Unit unable to provide informed consent prior to the intervention.