Gut Microbiome Signatures are Predictive of Infectious Risk Following Induction Therapy for Acute Myeloid Leukemia.

BACKGROUND: The majority of studies providing insights on the influence of the microbiome on the health of hematologic malignancy patients have concentrated on the transplant setting. Herein, we sought to assess the predictive capacity of the gastrointestinal microbiome and its relationship to clinical outcomes, with a specific focus on infection, in patients with acute myeloid leukemia (AML). METHODS: 16s rRNA based analysis was performed on oral swabs and stool samples obtained biweekly from baseline until neutrophil recovery following induction chemotherapy (IC) in 97 AML patients. Microbiome characteristics were correlated with clinical outcomes both during and after IC completion. RESULTS: At the start of IC, higher stool Shannon diversity (HR, 0.36; 95% CI, 0.18-0.74) and higher relative abundance of Porphyromonadaceae (HR, 0.36; 95% CI, 0.18-0.73) were associated with increased probability of remaining infection-free during neutropenia. A baseline stool Shannon diversity cut-off of 72 hours with a carbapenem, none of the patients had an infection with an extended spectrum beta-lactamase (ESBL) producing organism. Patients receiving carbapenems for >72hrs prior to neutrophil recovery had significantly lower α-diversity at neutrophil recovery (P=0.001) and were approximately 4 times more likely to have infection in the 90 days following neutrophil recovery (HR, 4.55; 95% CI, 1.73-11.93). CONCLUSIONS: Our results suggest that gut microbiome evaluation could assist with infectious risk stratification and that improved targeting of antibiotic administration during IC could decrease subsequent infectious complications of AML patients.