Adjunctive fecal microbiota transplantation in supportive oncology: Emerging indications and considerations in immunocompromised patients

Wardill, Hannah R.; Secombe, Kate R.; Bryant, Robert V.; Hazenberg, Mette D.; Costello, Samuel P

doi:10.1016/j.ebiom.2019.03.070

Cited by 59 publications

(52 citation statements)

References 71 publications

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“…Serious adverse reactions such as infection, peritonitis and disease relapse are not uncommon at 9.2%. It is important to note that the risk of death was estimated to be 3.5% [56]. However, when compared with FMT in immunocompentent patients, there was no statistical difference in adverse events and this study was likely confounded by the original indications for FMT.…”

Section: Fecal Transplantationmentioning

confidence: 78%

The Microbiota and Cancer Cachexia

Herremans

Riner

Cameron

et al. 2019

IJMS

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Cancer cachexia is a multifactorial syndrome defined by weight loss, muscle wasting, and systemic inflammation. It affects the majority of patients with advanced cancer and is associated with poor treatment response, early mortality and decreased quality of life. The microbiota has been implicated in cancer cachexia through pathways of systemic inflammation, gut barrier dysfunction and muscle wasting. The imbalance of the microbiota, known as dysbiosis, has been shown to influence cancer cachexia. Bacteria that play beneficial and detrimental roles in the disease pathogenesis have been identified. The phenotype of cancer cachexia is associated with decreased levels of Lactobacillales and increased levels of Enterobacteriaceae and Parabacteroides. Currently, there are no treatment options that demonstrate increased survival or the quality of life in patients suffering from cancer cachexia. Through the manipulation of beneficial bacteria in the gut microbiota, different treatment options have been explored. Prebiotics and probiotics have been shown to improve outcomes in animal models of cachexia. Expounding on this mechanism, fecal microbiota transplant (FMT) holds promise for a future treatment of cancer cachexia. Further research is necessary to address this detrimental disease process and improve the lives of patients suffering from cancer cachexia.

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Section: Fecal Transplantationmentioning

confidence: 78%

The Microbiota and Cancer Cachexia

Herremans

Riner

Cameron

et al. 2019

IJMS

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“…Our pilot study and other available research suggest that FMT can serve as a therapeutic option in treating steroid-refractory GI-GvHD [3,13,14,19].…”

Section: Introductionmentioning

confidence: 64%

Fecal Microbiota Transplantation for Grade IV Steroid Refractory GI-GvHD: Interim Results a Non-randomized, Open-label, Phase 1 Clinical Study

Zhao

Li²,

Zhou

et al. 2020

Preprint

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Background: Gastrointestinal (GI) tract graft-vs-host disease (GvHD) is a major cause of post-allo-HCT morbidity and mortality. Patients with steroid-refractory GI-GvHD face a poor prognosis and limited therapeutic options. Here, we report an interim analysis on the safety and efficacy of fecal microbiota transplantation (FMT) in treating steroid-refractory GI-GvHD.Methods: We did a non-randomized, open-label, phase 1 clinical study on patients with grade IV steroid-refractory GI-GvHD. FMT efficacy was evaluated using indexes of abdominal pain, diarrhea and bloody purulent stool at 14 and 21 days after the diagnosis of steroid-refractory GI-GvHD. The primary outcomes referred to clinical complete remission or partial remission. Secondary outcomes referred to EFS (event free survival) and OS (overall survival) at Day 90 and the end of the research. Safety was evaluated according to adverse events during FMT and the whole follow-up period. The study was registered with ClinicalTrials.gov as #NCT03148743.Results: A total of 56 patients with steroid-refractory GI-GvHD were enrolled. Of them, 24 patients with grade IV steroid-refractory GI-GvHD were assigned to FMT and 18 to the control group. The characteristics of the two group patients at baseline were similar. At Day 14 after FMT, 13 (54.2%) patients in FMT group and none (0%) of 18 control group achieved clinical remission (p<0.05), while 20(83%) patients in FMT group and 7(39%) in control group showed effective response (clinical remission+partial remission) (RR 7.86, 95% CI 1.88–32.9; p=0.005). At Day 21, the clinical remission was significantly greater in FMT group than in control group (14 (58.3%) of 24 vs 3(16%) of 18; RR 6.0, 95% CI 1.22–29.45; p=0.027). Within a follow up of 90 days, the FMT group showed better OS (HR, 7.0; 95% CI, 1.53-32.08; p=0.012). At the end of the research, the median survival time was >600 days in FMT group and 107 days in control group (HR, 4.73; 95% CI, 1.58-14.14; p=0.005). Both the EFS (HR, 0.24; 95% CI, 0.06-0.95; p=0.055) and OS (HR, 5.97; 95% CI, 1.52-23.43; p=0.01) kept increasing during the follow-up in FMT group. Overall, the mortality rate was lower in FMT group (HR, 5.97; 95% CI, 1.52-23.43; p=0.01). No difference was observed in the occurrence of other side effects, such as hemorrhagic cystitis, infection of bacteria & fungi, CMV&EBV, septicemia, TMA, cardiac events, thrombocytopenia and epilepsy.Conclusions: The diversity of intestinal microbiota can be affected by allo-HSCT. FMT is effective and safe in treating grade IV steroid refractory GI–GvHD.

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“…It is worth mentioning that an oral capsule seems to maintain the efficacy and safety of other routes, and is less invasive for the patient, 100 even if a substantial number of capsules is required to achieve the necessary microbial load. 101 Optimization of all these practical aspects still needs to be addressed in the future.…”

Section: Single Probioticsmentioning

confidence: 99%

“…Despite being deemed safe by all the case reports or case series revised in this study, there are still some concerns regarding the administration of living microorganisms to immunocompromised patients with altered intestinal permeability. 101,119 For example, infectious complications after FMT have been reported in other settings, 120,121 and they may be of key relevance regarding the risk and benefit balance of this procedure in HSCT recipients.…”

Section: Single Probioticsmentioning

confidence: 99%

Insights into the role of intestinal microbiota in hematopoietic stem-cell transplantation

Zama

Bossù

Leardini

et al. 2020

Therapeutic Advances in Hematology

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The gut microbiota (GM) is able to modulate the human immune system. The development of novel investigation methods has provided better characterization of the GM, increasing our knowledge of the role of GM in the context of hematopoietic stem-cell transplantation (HSCT). In particular, the GM influences the development of the major complications seen after HSCT, having an impact on overall survival. In fact, this evidence highlights the possible therapeutic implications of modulation of the GM during HSCT. Insights into the complex mechanisms and functions of the GM are essential for the rational design of these therapeutics. To date, preemptive and curative approaches have been tested. The current state of understanding of the impact of the GM on HSCT, and therapies targeting the GM balance is reviewed herein.

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Adjunctive fecal microbiota transplantation in supportive oncology: Emerging indications and considerations in immunocompromised patients

Cited by 59 publications

References 71 publications

The Microbiota and Cancer Cachexia

The Microbiota and Cancer Cachexia

Fecal Microbiota Transplantation for Grade IV Steroid Refractory GI-GvHD: Interim Results a Non-randomized, Open-label, Phase 1 Clinical Study

Insights into the role of intestinal microbiota in hematopoietic stem-cell transplantation

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