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

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. In this investigation we examined microbiome characteristics from baseline until neutrophil recovery following induction chemotherapy (IC) in 97 acute myeloid leukemia patients. We aimed to assess the predictive capacity of the gastrointestinal microbiome and its relationship to clinical outcomes, with a specific focus on infection. At the start of IC, higher Shannon diversity (HR, 0.36; P=0.005) and higher relative abundance of Porphyromonadaceae (HR, 0.36; P=0.005) were associated with increased probability of remaining infection free during neutropenia. We determined baseline Shannon diversity values <2 had the best sensitivity, positive, and negative predictive value for infectious complications during neutropenia. Longitudinal analyses of microbiome trajectories from baseline until neutrophil recovery found greater decreases in stool Shannon diversity among subjects who developed an infection in the 90 days post neutrophil recovery (P = 0.003). Additionally, carbapenem receipt for >72hrs resulted in significantly lower a-diversity at neutrophil recovery (P=0.001) and was associated with increased incidence of infection in the 90 days following neutrophil recovery (HR, 4.55; P=0.002). Similarly, days on treatment antibiotics during IC was inversely correlated with Shannon diversity at the end of sampling (r=-0.40, P<0.001) and the cumulative incidence of infections in the 90 days post neutrophil recovery (HR, 1.04; P=0.002). Our results suggest that gut microbiome evaluation could assist with infectious risk stratification and that antibiotic administration during IC may influence infectious complications of hematologic malignancy patients.