NCT03678493 - Fecal Microbiota Transplantation (FMT) & Acute myeloid leukemia (AML) (therapy-associated infections) or Allogeneic hematopoietic stem cell transplantation (allo HSCT) (therapy-associated infections)

Why is Fecal Microbiota Transplantation (FMT) considered for the treatment of Acute myeloid leukemia (AML) (therapy-associated infections) or Allogeneic hematopoietic stem cell transplantation (allo HSCT) (therapy-associated infections)?

• Gut microbiota injury in allogeneic hematopoietic cell transplantation (HCT) recipients and acute myeloid leukemia (AML) patients is linked to negative clinical outcomes.


• Studies indicate that fecal microbiota transplantation (FMT) can enhance various microbiome indices in these patients.


• It is uncertain if these microbiome improvements lead to better clinical outcomes (1)

What is being investigated in the randomized clinical trial NCT03678493?

• The trial is a randomized, clinical phase II trial.


• It investigates Fecal Microbiota Transplantation (FMT) or placebo.


• Participants are patients undergoing intensive induction chemotherapy for acute myeloid leukemia (AML) or Allo-HCT patients.


• Study treatment was administered after each course of antibacterial antibiotics.


• Up to three treatments were given within 3 months.


• Patients were monitored for 9 months


• Primary outcome measures:
  
  
  • Efficacy of FMT in AML Patients and Allo-HCT recipients: 4-month all-cause infection rate (1)
  
  
  
  

What are the results of the randomized clinical trial NCT03678493?

• HCT cohort: 74 patients

  
  
  • 4-month infection density:
    
    
    • FMT arm: 0.74 events per 100 patient-days
    
    
    • Placebo arm: 0.91 events per 100 patient-days
    
    
    
    
  
  
  • Infection rate ratio: 0.83
  
  
  • 95% Confidence Interval (CI): 0.48 to 1.42
  
  
  • P-value: 0.49
  
  
  
  



• AML cohort: 26 patients

  
  
  • 4-month infection density:
    
    
    • FMT arm: 0.93 events per 100 patient-days
    
    
    • Placebo arm: 1.25 events per 100 patient-days
    
    
    
    
  
  
  • Infection rate ratio: 0.74
  
  
  • 95% Confidence Interval (CI): 0.32 to 1.71
  
  
  • P-value: 0.48
  
  
  
  



• Unique donor bacterial sequences: 25%-30% of fecal microbiota post-FMT




• FMT effects:

  
  
  • Improved postantibiotic recovery of microbiota diversity
  
  
  • Restored depleted obligate anaerobic commensals
  
  
  • Reduced abundance of expanded genera: Enterococcus, Streptococcus, Veillonella, Dialister (1)
  
  
  
  

What is the conclusion of the authors?

• In allogeneic HCT recipients and AML patients, third-party FMT was safe.


• Third-party FMT improved intestinal dysbiosis.


• Third-party FMT did not reduce infections.


• Findings from this trial will guide future FMT trial development (1)

References

(1) Rashidi et al. 2023 Journal of Clinical Oncology 41(34): 5306-5319