Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML
PURPOSE: Gut microbiota injury in allogeneic hematopoietic cell transplantation (HCT) recipients and patients with AML has been associated with adverse clinical outcomes. Previous studies in these patients have shown improvements in various microbiome indices after fecal microbiota transplantation (FMT). However, whether microbiome improvements translate into improved clinical outcomes remains unclear. We examined this question in a randomized, double-blind, placebo-controlled phase II trial.
METHODS: Two independent cohorts of allogeneic HCT recipients and patients with AML receiving induction chemotherapy were randomly assigned in a 2:1 ratio to receive standardized oral encapsulated FMT versus placebo upon neutrophil recovery. After each course of antibacterial antibiotics, patients received a study treatment. Up to three treatments were administered within 3 months. The primary end point was 4-month all-cause infection rate. Patients were followed for 9 months.
RESULTS: In the HCT cohort (74 patients), 4-month infection density was 0.74 and 0.91 events per 100 patient-days in FMT and placebo arms, respectively (infection rate ratio, 0.83; 95% CI, 0.48 to 1.42; P = .49). In the AML cohort (26 patients), 4-month infection density was 0.93 in the FMT arm and 1.25 in the placebo arm, with an infection rate ratio of 0.74 (95% CI, 0.32 to 1.71; P = .48). Unique donor bacterial sequences comprised 25%-30% of the fecal microbiota after FMT. FMT improved postantibiotic recovery of microbiota diversity, restored several depleted obligate anaerobic commensals, and reduced the abundance of expanded genera Enterococcus, Streptococcus, Veillonella, and Dialister.
CONCLUSION: In allogeneic HCT recipients and patients with AML, third-party FMT was safe and ameliorated intestinal dysbiosis, but did not decrease infections. Novel findings from this trial will inform future development of FMT trials.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:41 |
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| Enthalten in: |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology - 41(2023), 34 vom: 01. Dez., Seite 5306-5319 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rashidi, Armin [VerfasserIn] |
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| Links: |
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| Themen: |
Clinical Trial, Phase II |
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| Anmerkungen: |
Date Completed 30.11.2023 Date Revised 05.12.2023 published: Print-Electronic ClinicalTrials.gov: NCT03678493 Citation Status MEDLINE |
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| doi: |
10.1200/JCO.22.02366 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357381009 |
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| 100 | 1 | |a Rashidi, Armin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 30.11.2023 | ||
| 500 | |a Date Revised 05.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03678493 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: Gut microbiota injury in allogeneic hematopoietic cell transplantation (HCT) recipients and patients with AML has been associated with adverse clinical outcomes. Previous studies in these patients have shown improvements in various microbiome indices after fecal microbiota transplantation (FMT). However, whether microbiome improvements translate into improved clinical outcomes remains unclear. We examined this question in a randomized, double-blind, placebo-controlled phase II trial | ||
| 520 | |a METHODS: Two independent cohorts of allogeneic HCT recipients and patients with AML receiving induction chemotherapy were randomly assigned in a 2:1 ratio to receive standardized oral encapsulated FMT versus placebo upon neutrophil recovery. After each course of antibacterial antibiotics, patients received a study treatment. Up to three treatments were administered within 3 months. The primary end point was 4-month all-cause infection rate. Patients were followed for 9 months | ||
| 520 | |a RESULTS: In the HCT cohort (74 patients), 4-month infection density was 0.74 and 0.91 events per 100 patient-days in FMT and placebo arms, respectively (infection rate ratio, 0.83; 95% CI, 0.48 to 1.42; P = .49). In the AML cohort (26 patients), 4-month infection density was 0.93 in the FMT arm and 1.25 in the placebo arm, with an infection rate ratio of 0.74 (95% CI, 0.32 to 1.71; P = .48). Unique donor bacterial sequences comprised 25%-30% of the fecal microbiota after FMT. FMT improved postantibiotic recovery of microbiota diversity, restored several depleted obligate anaerobic commensals, and reduced the abundance of expanded genera Enterococcus, Streptococcus, Veillonella, and Dialister | ||
| 520 | |a CONCLUSION: In allogeneic HCT recipients and patients with AML, third-party FMT was safe and ameliorated intestinal dysbiosis, but did not decrease infections. Novel findings from this trial will inform future development of FMT trials | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Ebadi, Maryam |e verfasserin |4 aut | |
| 700 | 1 | |a Rehman, Tauseef Ur |e verfasserin |4 aut | |
| 700 | 1 | |a Elhusseini, Heba |e verfasserin |4 aut | |
| 700 | 1 | |a Kazadi, David |e verfasserin |4 aut | |
| 700 | 1 | |a Halaweish, Hossam |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Mohammad H |e verfasserin |4 aut | |
| 700 | 1 | |a Hoeschen, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Qing |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Xianghua |e verfasserin |4 aut | |
| 700 | 1 | |a Kabage, Amanda J |e verfasserin |4 aut | |
| 700 | 1 | |a Lopez, Sharon |e verfasserin |4 aut | |
| 700 | 1 | |a Holtan, Shernan G |e verfasserin |4 aut | |
| 700 | 1 | |a Weisdorf, Daniel J |e verfasserin |4 aut | |
| 700 | 1 | |a Khoruts, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Staley, Christopher |e verfasserin |4 aut | |
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