Potential of Fecal Microbiota Transplantation to Prevent Acute GVHD : Analysis from a Phase II Trial
©2023 American Association for Cancer Research..
PURPOSE: Intestinal microbiota disruptions early after allogeneic hematopoietic cell transplantation have been associated with increased risk for acute GVHD (aGVHD). In our recent randomized phase II trial of oral, encapsulated, third-party fecal microbiota transplantation (FMT) versus placebo, FMT at the time of neutrophil recovery was safe and ameliorated dysbiosis. Here, we evaluated in post hoc analysis whether donor microbiota engraftment after FMT may protect against aGVHD.
EXPERIMENTAL DESIGN: We analyzed pre- and post-FMT stool samples and estimated donor microbiota engraftment (a preplanned secondary endpoint) by determining the fraction of post-FMT microbiota formed by unique donor taxa (donor microbiota fraction; dMf).
RESULTS: dMf was higher in patients who later developed grade I or no aGVHD (median 33.9%; range, 1.6%-74.3%) than those who developed grade II-IV aGVHD (median 25.3%; range, 2.2%-34.8%; P = 0.006). The cumulative incidence of grade II-IV aGVHD by day 180 was lower in the group with greater-than-median dMf than the group with less-than-median dMf [14.3% (95% confidence interval, CI, 2.1-37.5) vs. 76.9% (95% CI, 39.7-92.8), P = 0.008]. The only determinant of dMf in cross-validated least absolute shrinkage and selection operator (LASSO)-regularized regression was the patient's pre-FMT microbiota diversity (Pearson correlation coefficient -0.82, P = 1.6 × 10-9), indicating more potent microbiota modulation by FMT in patients with more severe dysbiosis. Microbiota network analysis revealed major rewiring including changes in the most central nodes, without emergence of keystone species, as a potential mechanism of FMT effect.
CONCLUSIONS: FMT may have protective effects against aGVHD, especially in patients with more severe microbiota disruptions.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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| Enthalten in: |
Clinical cancer research : an official journal of the American Association for Cancer Research - 29(2023), 23 vom: 01. Dez., Seite 4920-4929 |
| 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 04.12.2023 Date Revised 14.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1158/1078-0432.CCR-23-2369 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362817731 |
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| 245 | 1 | 0 | |a Potential of Fecal Microbiota Transplantation to Prevent Acute GVHD |b Analysis from a Phase II Trial |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 14.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ©2023 American Association for Cancer Research. | ||
| 520 | |a PURPOSE: Intestinal microbiota disruptions early after allogeneic hematopoietic cell transplantation have been associated with increased risk for acute GVHD (aGVHD). In our recent randomized phase II trial of oral, encapsulated, third-party fecal microbiota transplantation (FMT) versus placebo, FMT at the time of neutrophil recovery was safe and ameliorated dysbiosis. Here, we evaluated in post hoc analysis whether donor microbiota engraftment after FMT may protect against aGVHD | ||
| 520 | |a EXPERIMENTAL DESIGN: We analyzed pre- and post-FMT stool samples and estimated donor microbiota engraftment (a preplanned secondary endpoint) by determining the fraction of post-FMT microbiota formed by unique donor taxa (donor microbiota fraction; dMf) | ||
| 520 | |a RESULTS: dMf was higher in patients who later developed grade I or no aGVHD (median 33.9%; range, 1.6%-74.3%) than those who developed grade II-IV aGVHD (median 25.3%; range, 2.2%-34.8%; P = 0.006). The cumulative incidence of grade II-IV aGVHD by day 180 was lower in the group with greater-than-median dMf than the group with less-than-median dMf [14.3% (95% confidence interval, CI, 2.1-37.5) vs. 76.9% (95% CI, 39.7-92.8), P = 0.008]. The only determinant of dMf in cross-validated least absolute shrinkage and selection operator (LASSO)-regularized regression was the patient's pre-FMT microbiota diversity (Pearson correlation coefficient -0.82, P = 1.6 × 10-9), indicating more potent microbiota modulation by FMT in patients with more severe dysbiosis. Microbiota network analysis revealed major rewiring including changes in the most central nodes, without emergence of keystone species, as a potential mechanism of FMT effect | ||
| 520 | |a CONCLUSIONS: FMT may have protective effects against aGVHD, especially in patients with more severe microbiota disruptions | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 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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