Dysbiosis patterns during re-induction/salvage versus induction chemotherapy for acute leukemia

Armin Rashidi, Thomas Kaiser, Robin R Shields-Cutler, Carolyn Graiziger, Shernan G Holtan, Tauseef Ur Rehman, Justin Wasko, Daniel J Weisdorf, Gary M Dunny, Alexander Khoruts, Christopher M Staley

Research output: Contribution to journalArticle

Abstract

Acute leukemia (AL) patients undergoing intensive induction chemotherapy develop severe gut dysbiosis, placing them at heightened risk for infectious complications. Some AL patients will undergo “repeat therapy” (re-induction or salvage) due to persistent or relapsed disease. We hypothesized that prior injury to the microbiome during induction may influence dysbiosis patterns during repeat therapy. To test this hypothesis, we analyzed the bacterial microbiome profiles of thrice-weekly stool samples from 20 intensively treated AL patients (first induction: 13, repeat therapy: 7) by 16S rRNA sequencing. In mixed-effects modeling, repeat therapy was a significant predictor of Enterococcus expansion (P = 0.006), independently of antibiotic exposure, disease type, feeding mode, and week of chemotherapy. Bayesian analysis of longitudinal data demonstrated larger departures of microbial communities from the pre-chemotherapy baseline during repeat therapy compared to induction. This increased ecosystem instability during repeat therapy possibly impairs colonization resistance and increases vulnerability to Enterococcus outgrowth. Microbiota restoration therapies at the end of induction or before starting subsequent therapy warrant investigation.

Original languageEnglish (US)
Article number6083
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Dysbiosis
Induction Chemotherapy
Leukemia
Microbiota
Enterococcus
Therapeutics
Drug Therapy
Bayes Theorem
Ecosystem
Anti-Bacterial Agents

PubMed: MeSH publication types

  • Journal Article

Cite this

Dysbiosis patterns during re-induction/salvage versus induction chemotherapy for acute leukemia. / Rashidi, Armin; Kaiser, Thomas; Shields-Cutler, Robin R; Graiziger, Carolyn; Holtan, Shernan G; Rehman, Tauseef Ur; Wasko, Justin; Weisdorf, Daniel J; Dunny, Gary M; Khoruts, Alexander; Staley, Christopher M.

In: Scientific reports, Vol. 9, No. 1, 6083, 01.12.2019.

Research output: Contribution to journalArticle

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abstract = "Acute leukemia (AL) patients undergoing intensive induction chemotherapy develop severe gut dysbiosis, placing them at heightened risk for infectious complications. Some AL patients will undergo “repeat therapy” (re-induction or salvage) due to persistent or relapsed disease. We hypothesized that prior injury to the microbiome during induction may influence dysbiosis patterns during repeat therapy. To test this hypothesis, we analyzed the bacterial microbiome profiles of thrice-weekly stool samples from 20 intensively treated AL patients (first induction: 13, repeat therapy: 7) by 16S rRNA sequencing. In mixed-effects modeling, repeat therapy was a significant predictor of Enterococcus expansion (P = 0.006), independently of antibiotic exposure, disease type, feeding mode, and week of chemotherapy. Bayesian analysis of longitudinal data demonstrated larger departures of microbial communities from the pre-chemotherapy baseline during repeat therapy compared to induction. This increased ecosystem instability during repeat therapy possibly impairs colonization resistance and increases vulnerability to Enterococcus outgrowth. Microbiota restoration therapies at the end of induction or before starting subsequent therapy warrant investigation.",
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AU - Rashidi, Armin

AU - Kaiser, Thomas

AU - Shields-Cutler, Robin R

AU - Graiziger, Carolyn

AU - Holtan, Shernan G

AU - Rehman, Tauseef Ur

AU - Wasko, Justin

AU - Weisdorf, Daniel J

AU - Dunny, Gary M

AU - Khoruts, Alexander

AU - Staley, Christopher M

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