Page 201 - 2020_11-Haematologica-web

Letters to the Editor
resulted in 80% (4 of 5) MDR decolonization within one week after the procedure. Since repeated FMT could increase the chances of durable decolonization, this pro- tocol might be indicated for patients with a predicted long-lasting immunosuppression or in the presence of other risk factors for recurrent infections.
Our data suggest FMT safety and feasibility in pediatric patients with hematologic disorders immediately before the aplastic phase of HSCT. Four patients did not experi- ence serious AE, while patient 1 suffered from an episode of sepsis (from the same pathogen for which he received FMT) 17 days after the procedure. In all patients, only few symptoms related to the FMT procedure were recorded, all being transient and easily controlled by symptomatic drugs. Recently, two episodes of life-threat- ening/fatal sepsis due to ESBL E. coli were reported in adults undergoing FMT in two different clinical trials.10 However, based on the last European Consensus11 and national recommendations, extensive MDR bacteria test- ing is a cornerstone of donor screening in our institution.
Antibiotic-driven decolonization is a matter of discus- sion in the context of FMT. Oral colistin was proposed as a treatment to decolonize gut microbiota MDR bacteria before FMT. Stoma et al. randomized 62 adult hemato- logic patients colonized by MDR bacteria to receive oral colistin or placebo for 14 days,12 showing improved decolonization at the end of treatment not persisting 1 week later; moreover, the incidence of bloodstream infections in the case/control groups was similar. Based on these results, oral colistin was administered to four of our patients before FMT to provide an “induction” thera- py followed by “consolidation” through FMT, with the idea of improving donor microbiota “engraftment”. From our data, it seems that, at early time points after FMT preceded by oral colistin administration, the gut micro- biota composition was more similar to that of the FMT- donor. However, more patients are needed to assess the effective role of oral colistin as FMT preparation on microbiome composition.
After the exclusion of related donors, who were not eligible because of the presence of pathogens/commen- sals at screening, a healthy unrelated volunteer was selected, in agreement with previous literature. Indeed, systematic reviews/meta-analysis13 in patients receiving FMT for C. difficile infection did not report any difference in outcomes based on donor selection. Donor (unrelated- versus-related) and sample (fresh-versus-frozen) types are emerging topics, since availability of stool banks could widen and facilitate FMT,14 especially under emergency regimes. We used both fresh and frozen emulsions from the Ospedale Pediatrico Bambino Gesù FMT bank. Since the screening of potential donors can require weeks, the use of frozen material can reduce the time to perform the procedure.
We administered the stool preparation during EGDS directly in the duodenum. Battipaglia et al. used enema as a way of administration, reporting good rate of decolo- nization.9 We preferred upper gastrointestinal tract (GI) administration to extend as much as possible the effect of FMT to the whole intestine.15 Current literature reports the administration via upper GI in most cases.
Results obtained in 4 of 5 patients suggest that micro- biota changes following FMT occur after T1, when its composition is still similar to T0. In particular, the recip- ients’ microbiota seems to be colonized by donor bacteria starting from one week after the procedure. These simi- larities are not long-lasting. Indeed, at approximately 10 days after FMT, the recipients' microbiota display a con- sistently different profile both from the donor and the
recipient's T0. These changes could be secondary to the conditioning regimen and/or antibiotic prophylaxis. Therefore, boosts of FMT should be considered within one week after first procedure to consolidate MDR decol- onization (e.g., leaving in place a naso-jejunale tube in pediatric patients).
From an ecological point of view, 1 day after FMT we recorded the overgrowth of facultative anaerobes and aerobes, as Enterobacteriaceae, probably promoted by the O2-conditions generated during the FMT emulsion. Afterward, the slow growth of strict anaerobes from donor reduced the O2-conditions suppressing the relative amount of Enterobacteriaceae. Thus, we suggest that future FMT emulsion preparations should be performed under anaerobic conditions to reduce the Enterobacteriaceae overgrowth favoring MDR species.
Main limitations of this report are: (i) its non-prospec- tive nature; (ii) some heterogeneity of the FMT protocol (e.g., use of colistin, fresh/frozen material); (iii) the small number of cases, all affecting the possibility to draw firm conclusions.
In conclusion, we showed that FMT for MDR-decolo- nization of pediatric hematologic patients is safe, feasi- ble, and effective in the short-term. Stool preparations from universal donors, starting from either fresh or frozen material, are readily available and safe, thus paving the way to stool banks. Further studies enrolling more populations are needed to confirm these prelimi- nary data and to improve effectiveness of decolonization and infection clearance during the HSCT window.
Pietro Merli,1* Lorenza Putignani,2* Annalisa Ruggeri,1 Federica Del Chierico,3 Livia Gargiullo,4 Federica Galaverna,1 Stefania Gaspari,1 Daria Pagliara,1 Alessandra Russo,3 Stefania Pane,5 Luisa Strocchio,1 Mattia Algeri,1
Francesca Rea,6 Erminia Francesca Romeo,6 Paola Bernaschi,7 Andrea Onetti Muda,8 Bruno Dallapiccola9 and
Franco Locatelli1,10
1Department of Hematology/Oncology, Cellular and Gene Therapy, Bambino Gesù Children’s Hospital; 2Unit of Parasitology and Unit of Human Microbiome, Bambino Gesù Children’s Hospital; 3Unit of Human Microbiome, Bambino Gesù Children’s Hospital; 4Unit of Immunology and Infectious Diseases, University-Hospital Pediatric
5
Department, Bambino Gesù Children's Hospital; Unit of Parasitology,
Bambino Gesù Children's Hospital; 6Digestive Endoscopy and Surgery Unit, Bambino Gesù Children's Hospital; 7Unit of Microbiology, Bambino Gesù Children’s Hospital; 8Department of Laboratories, Bambino Gesù Children's Hospital; 9Scientific Directorate, Bambino Gesù Children's Hospital and 10Sapienza, University of Rome,
Rome, Italy
*PM and LP contributed equally as co-first authors.
Correspondence:
PIETRO MERLI - pietro.merli@opbg.net
doi:10.3324/haematol.2019.244210
Funding: this study was partially supported by the Italian Ministero della Salute (Bando Ricerca Finalizzata 2013, Giovani Ricercatori section, code GR-2013-02357136 to PM).
Acknowledgments: we wish to thank the FMT Committee of Bambino Gesù Children’s Hospital and research Institute (Giulia Angelino, Marta Argentieri, Luigi Dall’Oglio, Patrizia D’Argenio, Paola De Angelis, Simona Faraci, Andrea Finocchi, Gianluca Foglietta, Sandra Martino, Giulia Marucci, Andrea Quagliariello, Giuliano Torre, Filippo Torroni, Valerio Nobili).
References
1. Cammarota G, Ianiro G, Tilg H, et al. European consensus confer- ence on faecal microbiota transplantation in clinical practice. Gut.
haematologica | 2020; 105(11)
2689