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Background Enterococcus intestinal domination (EID), a state of dysbiosis wherein enterococci comprise ≥30% abundance within the microbiota, has been associated with Enterococcus bacteremia, graft-versus-host disease, and mortality in the allogeneic hematopoietic stem cell transplant (allo HCT) population. The acute leukemia (AL) chemotherapy population includes patients receiving intensive chemotherapy, but not all patients go on to have an allo HCT. The impact of EID on outcomes including mortality in the AL chemotherapy population is unknown. Methods Microbiota composition from weekly stool samples was analyzed using 16S ribosomal RNA gene sequencing. Patients were analyzed in 2 cohorts: AL chemotherapy cohort and allo HCT cohort. α -diversity and richness were calculated. Kaplan-Meier analysis was used to analyze mortality. Results A total of 929 stool samples were collected from 139 patients. Both allo HCT and AL cohorts had a decline in α-diversity and richness over the course of treatment that tended not to return to baseline months later. EID was observed in at least 1 sample in 36% of allo HCT patients and 49% of AL patients. Patients with observed EID had lower α-diversity over time. Similar to the HCT cohort, AL patients with EID had reduced overall survival. We identified 4 other genera that were commonly found in ≥30% relative abundance within the microbiota, but none were associated with mortality. In fact, in allo HCT, Bacteroides abundance ≥30% was associated with improved survival. Conclusions EID is associated with increased all-cause mortality in HCT and AL cohorts. Unlike EID, relative abundance ≥30% by other genera is not associated with increased all-cause mortality. [ABSTRACT FROM AUTHOR]