Repeated Courses of Orally Administered Fecal Microbiota Transplantation for the Treatment of Steroid Resistant and Steroid Dependent Intestinal Acute Graft Vs. Host Disease: A Pilot Study (NCT 03214289)
Abstract:Background: Steroid-resistant (SR) intestinal acute graft versus host disease (aGVHD) is a devastating complication of allogeneic hematopoietic stem cell transplantation. Preliminary reports suggest that fecal microbiota transplantation (FMT) administered through a nasogastric tube or colonoscopy may be an effective treatment. We report the results of a single-arm pilot study (NCT 03214289) using FMT in capsules to treat SR or steroid dependent (SD) intestinal aGVHD.
Methods: The primary outcome… Show more
“…Recurrent CDI Webb et al 71 7 No recurrence in 6 Moss et al 72 6 No recurrence in 4 Bluestone et al 73 3 99 1 CR Zhang et all 100 1 CR Zhong et al 101 1 CR Shouval et al 102…”
Section: Therapeuticmentioning
confidence: 99%
“…Response to treatment was seen within a median of 14 days (range: 3-28), with a median of two FMT (range: 1-7), and a median of 7 days between treatments (range: 2-60). 46,[98][99][100][101][102][103][104][105][106] Infectious complications occurred in 11 patients. Two had sepsis with bacteria not originating from FMT, 102 and one patient developed diarrhea due to Norovirus that was traced to FMT.…”
Section: Can Fecal Microbiota Transplantation Mitigate Prevailing Acumentioning
confidence: 99%
“…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 treatment and in non-randomized FMT studies. 46,[98][99][100][101][102][103][104][105][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 activity 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.…”
Section: Practical Considerations For Fecal Microbiota Transplantatiomentioning
Outcomes of allogeneic hematopoietic stem cell transplantation (allo- HSCT) have improved in the recent decade; however, infections and graft-versus-host disease remain two leading complications significantly contributing to early transplant-related mortality. In past years, the human intestinal microbial composition (microbiota) has been found to be associated with various disease states, including cancer, response to cancer immunotherapy and to modulate the gut innate and adaptive immune response. In the setting of allo-HSCT, the intestinal microbiota diversity and composition appear to have an impact on infection risk, mortality and overall survival. Microbial metabolites have been shown to contribute to the health and integrity of intestinal epithelial cells during inflammation, thus mitigating graft-versus-host disease in animal models. While the cause-andeffect relationship between the intestinal microbiota and transplant-associated complications has not yet been fully elucidated, the above findings have already resulted in the implementation of various interventions aiming to restore the intestinal microbiota diversity and composition. Among others, these interventions include the administration of fecal microbiota transplantation. The present review, based on published data, is intended to define the role of the latter approach in the setting of allo-HSCT.
“…Recurrent CDI Webb et al 71 7 No recurrence in 6 Moss et al 72 6 No recurrence in 4 Bluestone et al 73 3 99 1 CR Zhang et all 100 1 CR Zhong et al 101 1 CR Shouval et al 102…”
Section: Therapeuticmentioning
confidence: 99%
“…Response to treatment was seen within a median of 14 days (range: 3-28), with a median of two FMT (range: 1-7), and a median of 7 days between treatments (range: 2-60). 46,[98][99][100][101][102][103][104][105][106] Infectious complications occurred in 11 patients. Two had sepsis with bacteria not originating from FMT, 102 and one patient developed diarrhea due to Norovirus that was traced to FMT.…”
Section: Can Fecal Microbiota Transplantation Mitigate Prevailing Acumentioning
confidence: 99%
“…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 treatment and in non-randomized FMT studies. 46,[98][99][100][101][102][103][104][105][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 activity 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.…”
Section: Practical Considerations For Fecal Microbiota Transplantatiomentioning
Outcomes of allogeneic hematopoietic stem cell transplantation (allo- HSCT) have improved in the recent decade; however, infections and graft-versus-host disease remain two leading complications significantly contributing to early transplant-related mortality. In past years, the human intestinal microbial composition (microbiota) has been found to be associated with various disease states, including cancer, response to cancer immunotherapy and to modulate the gut innate and adaptive immune response. In the setting of allo-HSCT, the intestinal microbiota diversity and composition appear to have an impact on infection risk, mortality and overall survival. Microbial metabolites have been shown to contribute to the health and integrity of intestinal epithelial cells during inflammation, thus mitigating graft-versus-host disease in animal models. While the cause-andeffect relationship between the intestinal microbiota and transplant-associated complications has not yet been fully elucidated, the above findings have already resulted in the implementation of various interventions aiming to restore the intestinal microbiota diversity and composition. Among others, these interventions include the administration of fecal microbiota transplantation. The present review, based on published data, is intended to define the role of the latter approach in the setting of allo-HSCT.
“…One paper was excluded because the etiology of diarrhea, reported as the reason for FMT, was not clear [ 32 ]. Of the 23 studies assessed, 15 were case reports or retrospective case series [ 30 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ], seven were prospective cohorts [ 47 , 48 , 49 , 50 , 51 , 52 , 53 ], while only one completed randomized controlled trial was found in the literature [ 54 ].…”
Section: Resultsmentioning
confidence: 99%
“…After FMT, the introduction of new bacteria and an increase in microbial diversity was found in the recipient’s stool, with a strong reduction in the rate of bacterial dominance. Only two patients achieved complete remission, and one a partial response [ 50 ]. In the case report by Mao et al, after two cycles of oral FMT capsules from unrelated donor, intestinal aGvHD was gradually controlled and did not recur during the two-month follow-up.…”
The disruption of gut microbiota eubiosis has been linked to major complications in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Various strategies have been developed to reduce dysbiosis and related complications. Fecal microbiota transplantation (FMT) consists of the infusion of fecal matter from a healthy donor to restore impaired intestinal homeostasis, and could be applied in the allo-HSCT setting. We conducted a systematic review of studies addressing the use of FMT in allo-HSCT patients. In the 23 papers included in the qualitative synthesis, FMT was used for the treatment of recurrent Clostridioides difficile infections or as a therapeutic strategy for steroid-resistant gut aGvHD. FMT was also performed with a preventive aim (e.g., to decolonize from antibiotic-resistant bacteria). Additional knowledge on the biological mechanisms underlying clinical findings is needed in order to employ FMT in clinical practice. There is also concern regarding the administration of microbial consortia in immune-compromised patients with altered gut permeability. Therefore, the safety profile and efficacy of the procedure must be determined to better assess the role of FMT in allo-HSCT recipients.
Allogeneic hematopoietic stem cell transplantation is one of the most effective treatment strategies for leukemia, lymphoma, and other hematologic malignancies. However, graft‐versus‐host disease (GVHD) can significantly reduce the survival rate and quality of life of patients after transplantation, and is therefore the greatest obstacle to transplantation. The recent development of new technologies, including high‐throughput sequencing, metabolomics, and others, has facilitated great progress in understanding the complex interactions between gut microbiota, microbiota‐derived metabolites, and the host. Of these interactions, the relationship between gut microbiota, microbial‐associated metabolites, and GVHD has been most intensively researched. Studies have shown that GVHD patients often suffer from gut microbiota dysbiosis, which mainly manifests as decreased microbial diversity and changes in microbial composition and microbiota‐derived metabolites, both of which are significant predictors of poor prognosis in GVHD patients. Therefore, the purpose of this review is to summarize what is known regarding changes in gut microbiota and microbiota‐derived metabolites in GVHD, their relationship to GVHD prognosis, and corresponding clinical strategies designed to prevent microbial dysregulation and facilitate treatment of GVHD.
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