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Fecal microbial transplant in HSCT
donor (a family member, an unrelated donor, or pooled stool from several unrelated donors).
As for autologous FMT, it has not been tested in the set- ting of aGvHD treatment. Since the microbiota composi- tion of a patient is already disrupted prior to HSCT, using such stool in FMT preparation to be applied for diversity restoration may not be effective. In order to circumvent this problem, in AML patients, we recommend freezing self-stool before the beginning of induction chemotherapy.
In CDI, both fresh and frozen FMT have been shown to be efficient116 as have been the two delivery routes − colonoscopy and oral capsules.117 While there are no data pointing to the superiority of either method of preparation or administration for aGvHD treatment, frozen samples from a stool bank allow FMT to be readily available for immediate use without the need to wait for donor screen- ing and FMT collection.
The basic principles of FMT preparation include weigh- ing the sample, suspension in sterile solution (saline), adding glycerol in case the FMT is planned for freezing and storing, homogenization, filtering and aliquoting the sus-
Table 3. Practical aspects of fecal microbiota transplantation. FMT stool bank114
pension for fresh use or freezing (Table 3). The FMT prod- uct should be registered and labeled.114
Based on the available data (Table 2) we suggest evaluat- ing clinical response at 7-14 days after FMT administration. If no response or only partial response is achieved, we rec- ommend administering a second dose of FMT. Whether in such cases the use of FMT from another donor could pro- vide a superior outcome is yet to be determined. In general, in order to consider FMT as an efficacious therapeutic approach for SR GI aGvHD management, an overall response rate of around 60-70%, with a complete response rate of 30-50% should be a desired target, as these rates are achieved with the use of the approved ruxolitinib treat- ment and in non-randomized FMT studies.46,98-106,110
As for the antibiotic treatment peri-FMT, if feasible, 24- 48 hours prior to FMT, systemic antibiotics should be stopped or replaced by one with less anti-anaerobic activi- ty such as rifaximin for prophylaxis or cefepime for febrile neutropenic treatment.46,98,99
Microbiome sequencing of donor and patient samples could help interpreting clinical outcomes. It could also be
- Center’s own bank
- Acquiring FMT from stool banks of other centers or from a universal stool bank
Regulations114
- Set by the designated authority in each country
- Follow international guidelines and recommendations
- If local directives are not available, the center scientific committee should establish regulatory protocols - FMT for SR GI aGvHD should be given within the setting of a clinical trial
FMT donor screening114*
Medical history for infections and risk for infections:
- HIV, hepatitis C, hepatitis B, syphilis, HTLV, other infections, malaria, tuberculosis, illegal drug use, unprotected sex, tissue/organ transplant, recent hospitalization, travel to high risk endemic countries, tattoo, piercing, earing, recent intestinal infection, recent vaccinations with live attenuated virus, blood transfusion, therapy with growth hormone.
Medical history for conditions and medications with risk for microbiota perturbation:
- Chronic gastrointestinal disease (e.g., inflammatory bowel disease, celiac disease), autoimmune disease, cancer, recent GI symptoms
(e.g., diarrhea), neurologic disorders, psychiatric disorders, obesity, metabolic syndrome, diabetes, first degree relative with early colon cancer or polyposis. Antibiotic treatment in recent 3 months, chemotherapy, immunotherapy, prolonged use of proton-pump inhibitors, use of probiotics.
Blood tests:
- Hepatitis A, B and C, HTLV, HIV, treponema pallidum, strongyloides stercoralis, NAT for hepatitis B, C and HIV, ANCA (P and C), IgA antibodies level, anti-transglutaminase antibodies, antinuclear antibody, ASCA, liver enzymes, creatinine, calcium, albumin, cholesterol, triglycerides, complete blood count, thyroid function test.
Stool tests:
- Stool culture for Shigella, Salmonella and Campylobacter, direct smear for parasites from different occasions, Clostridium difficile antigen, vancomycin-resistant Enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), extended spectrum β lactamase producing Enterobacteriaceae (ESBL), *Biofire (Biofire FilmArray) multiplex PCR for Yersinia enterocolitica, EAEC (Enteroaggregative E. coli), EPEC (Enteropathogenic E. coli), ETEC (Enterotoxigenic E. coli), STEC (Shiga-like toxin producing E. coli stx1/stx2),
E. coli O157, Shigella / EIEC (Enteroinvasive E. coli), Cryptosporidium, Cyclospora cayetanensis, Entamoeba histolytica, Giardia lamblia, Adenovirus F 40/41, Astrovirus, Norovirus, Rotavirus A, Sapovirus, Campylobacter, Clostridium difficile toxins A and B, Plesiomonas shigelloides, Salmonella, Vibrio parahaemolyticus and vulnificus, Vibrio cholerae.
Special considerations:
- Cytomegalovirus and Epstein-Barr virus serology (IgM and IgG) when administration to immunocompromised patients is planned.114
- Patients with severe food allergy should receive FMT from a donor who will avoid the allergy causing food for 72 hours prior to donation.* - SARS-CoV-2 screening120 following the FDA safety alert.121
Consent:
- Both donors and patients should sign appropriate informed consent.
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