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I. Henig et al.
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FMT source122
- Fresh versus frozen: frozen is ready for immediate use.
- Unrelated donor, pooled stool from many unrelated donors, related donor, autologous collected while the patient was still healthy.
FMT preparation and storage114,122* (in brief)
- Donor stool collected into a sterile plastic container.
- If not done on site, it should be kept at -4°C until processing.
- Stool processing and storage should be done within 6 hours from collection.
- Processing should be done in a sterile hood
- Weigh the stool (25 g minimum for lower GI FMT and 12.5 g for upper GI FMT).
- Mix with sterile saline, homogenize, filter and centrifuge.
- Re-suspend the pellet with saline.
- If stored frozen, add glycerol to a concentration of 10%.
- Aliquot and label according to way of administration (capsules, tubes)
- Frozen FMT should be kept at -80°C and preferably used within 1 year from collection.
FMT administration114,122*
FMT preparation:
- Fresh FMT is given within 6-8 hours from collection.
- Frozen FMT is thawed at 37°C water bath and administered within 4-6 hours. - Frozen capsules, thawed at room temperature for a few minutes.
Method of administration:
- Upper GI – gastroduodenoscopy, nasogastric tube, nasoduodenal tube, capsules. - Lower GI - colonoscopy, enema.
Special considerations:
- If possible, to stop antibiotic treatment 24-48 hours prior to administration.
- Or replace current antibiotics with less anti-anaerobic antibiotics (e.g., rifaximin, cefepime)
Monitoring for clinical response in GI aGVHD
- In 7-14 days after administration.
- In case of no response or partial response, consider a second dose.
Stool sampling for later sequencing (16S ribosomal RNA sequencing or other)
From donor:
- A sample from the collected stool of each batch of donation.
From patient:
- A sample obtained before FMT, 1 week, 2 weeks and 4 weeks after FMT, at relapse/progression of GI aGvHD. Monitoring for adverse events122*
Commonly reported:
- Aspiration (in upper GI administration), nausea, vomiting, constipation, diarrhea, bloating, abdominal pain, adverse events caused by the nasogastric tube insertion or colonoscopy procedure, fever.
Infections:
- Diarrhea, colitis, bacteremia, pneumonia.
*National and Institutional guidelines.FMT:fecal microbiota transplantation,SR:steroid refractory,GI:gastrointestinal,aGvHD:acute graft-versus-host disease,HIV:human immun- odeficiency virus,HTLV:humanT-cell leukemia virus,NAT:nucleic acid test,ANCA:anti-neutrophil cytoplasmic antibodies,ASCA:anti- saccharomyces cerevisiae antibodies,CMV: cytomegalovirus, EBV: Epstein-Bar virus.
valuable in distinguishing between the donor and the recipient as the source of post-FMT infection. However, currently there are no data suggesting that patient stool sequencing prior to FMT could guide its administration or affect the outcome. Therefore, given that the primary out- come should be the clinical response to treatment we rec- ommend treating SR GI aGvHD patients with FMT even if the microbiome analysis is not available. Nonetheless, we do suggest storing stool samples from the donor and the patient (before and after FMT) for later sequencing if it becomes available.
Further accumulation of data on FMT for SR GI aGvHD will allow wider and more efficient application of this treatment approach.
Open challenges and future directions
Disruption of the intestinal microbiome during allo- HSCT is a multifaceted process with a cause-and-effect relationship between multiple factors such as condition- ing, diet and antibiotic treatment. Lately, FMT has emerged as an intervention that can facilitate microbio- me recovery and potentially intervene with the above interplay (Figure 1). The intestinal microbial disruption before and during allo-HSCT is clearly associated with transplant-related outcomes, mainly acute GvHD and mortality, and pre-clinical data demonstrate the key role of the intestinal microbiota in protecting the gut from inflammatory damage and in regulating the innate immune system to maintain a more tolerant state.118
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haematologica | 2021; 106(4)