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Fecal microbial transplant in HSCT
Table 2. Clinical trials of fecal microbiota transplant in allogeneic hematopoietic stem cell transplantation.
FMT aim Study (ref.) or ‡NCT number Number of patients
Prophylactic
Reduce pathogenic bacteria colonization pre-transplantation
Malard et al.66 20 Battipaglia et al.64 4
Innes et al.65 1
Restore microbiome diversity post-transplantation
Outcomes
Restoration of diversity, reduction in antibiotic-resistant gene copy count
All decolonized
All decolonized
Increase in diversity Increase in diversity
No recurrence in 6 No recurrence in 4 No recurrence in 1
2CR,1PR,3died 3CR,1PR
CR
CR
CR
2CR,1PR,4died 3CR,1VGPR,2PR,3died 8 ORR, 2 relapsed, 4 died 11 CR, 5 relapsed
5 ORR, CR 4,SD1
Response and OS Response Response Response Response and OS
Therapeutic
Recurrent CDI
Defillip et al.25 13 Taur et al.53 Random:
FMT 14 vs. control 11
Webb et al.71 7 Moss et al.72 6 Bluestone et al.73 3
Steroid refractory/dependent acute GI GvHD
Spindelboeck et al.198 3 Kakihana et al.l46 4 Kaito et al.99 1 Zhang et al.l100 1 Zhong et al.101 1 Shouval et al.102 7 Malard et al.103 8 Qi et al.104 8 van Lier et al.105 15 Bilinski et al.106 10
¶Ongoing clinical trials in GI acute GvHD
NCT04269850 ¥20 NCT03819803 ¥15 NCT03812705 ¥30 NCT04285424 ¥30 NCT03359980 (HERACLES trial) ¥32
FMT: fecal microbiota transplant; ‡NCT number: clinicaltrials.gov Identifier. ¶Recruiting or completed from ClinicalTrials.gov; ¥Estimated enrollment; GI: gastrointestinal tract; GvHD: graft-versus-host disease; CR: complete remission; PR: partial remission;VGPR: very good partial remission; SD: stable disease; OS: overall survival; ORR: overall response rate.
patient has pre-transplant intestinal microbiota disruption and assumed colonization by MDR bacteria and probably by Clostridium difficile. His risk for aGvHD is high, since he has undergone allo-HSCT from a mismatched unrelated donor. Quinolone prophylaxis and meropenem treatment for BSI have further disrupted his intestinal microbiota. The existence of pre-transplant microbiota disruption, mainly attributed to the use of broad-spectrum antibi- otics during intensive chemotherapy, is associated with increased TRM, shorter OS and GvHD-related mortality. Pre-transplant FMT can potentially enrich the microbio- me diversity and eradicate MDR bacteria or Clostridium difficile; however, without controlling such factors as antibiotic prophylaxis and the type of systemic antibiotic therapy employed, the intervention by FMT may not completely achieve its goals.
So far, no data are available regarding a clinical benefit of prophylactic pre-transplant FMT.
While an association between peri-engraftment micro- biome low diversity and patient outcome is established, implying potential feasibility of FMT use at that stage, data regarding FMT application before engraftment are not
available, and for safety reasons this approach will proba- bly not be attempted. Results of several small-scale studies suggest safety and feasibility of post-engraftment FMT in restoring microbiome diversity (Table 2); however, it remains unknown if this strategy could decrease the risk for aGvHD-related mortality and TRM.
As for dietary interventions at this period, their efficacy is still under investigation. Choosing a different antibiotic prophylaxis, such as rifaximin and systemic antibiotics such as cefepime, looks promising. Nevertheless, new strategies need to be tested to prove their non-inferiority in OS85 and to establish less disruption for the microbiome (clinicaltrials gov. Identifier: 03078010), especially since fourth-generation cephalosporins have been found in one study to be associated with an increased risk for aGvHD.97
Case 1: recommendations
In this case, based on the currently available data, we do not recommend prophylactic administration of pre- transplant or post-engraftment FMT.
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