The role of the gastrointestinal microbiome in infectious complications during induction chemotherapy for acute myeloid leukemia

• Published in: Cancer Vol. 122; no. 14; pp. 2186 - 2196
• Main Authors: Galloway‐Peña, Jessica R., Smith, Daniel P., Sahasrabhojane, Pranoti, Ajami, Nadim J., Wadsworth, W. Duncan, Daver, Naval G., Chemaly, Roy F., Marsh, Lisa, Ghantoji, Shashank S., Pemmaraju, Naveen, Garcia‐Manero, Guillermo, Rezvani, Katayoun, Alousi, Amin M., Wargo, Jennifer A., Shpall, Elizabeth J., Futreal, Phillip A., Guindani, Michele, Petrosino, Joseph F., Kontoyiannis, Dimitrios P., Shelburne, Samuel A.
• Format: Journal Article
• Language: English
• Published: United States 15.07.2016
• Subjects: acute myeloid leukemia; Adult; Aged; Biodiversity; Female; gastrointestinal; Gastrointestinal Microbiome; High-Throughput Nucleotide Sequencing; Humans; induction chemotherapy; Induction Chemotherapy - adverse effects; Infection - diagnosis; Infection - etiology; infectious complications; Leukemia, Myeloid, Acute - complications; Leukemia, Myeloid, Acute - drug therapy; Male; Metagenome; Metagenomics - methods; microbiome; Middle Aged; Prognosis; RNA, Ribosomal, 16S - genetics; Young Adult; gastrointestinal; acute myeloid leukemia; induction chemotherapy; microbiome; infectious complications
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.30039

BACKGROUND Despite increasing data on the impact of the microbiome on cancer, the dynamics and role of the microbiome in infection during therapy for acute myelogenous leukemia (AML) are unknown. Therefore, the authors sought to determine correlations between microbiome composition and infectious outcomes in patients with AML who were receiving induction chemotherapy (IC). METHODS Buccal and fecal specimens (478 samples) were collected twice weekly from 34 patients with AML who were undergoing IC. Oral and stool microbiomes were characterized by 16S ribosomal RNA V4 sequencing using an Illumina MiSeq system. Microbial diversity and genera composition were associated with clinical outcomes. RESULTS Baseline stool α‐diversity was significantly lower in patients who developed infections during IC compared with those who did not (P = .047). Significant decreases in both oral and stool microbial α‐diversity were observed over the course of IC, with a linear correlation between α‐diversity change at the 2 sites (P = .02). Loss of both oral and stool α‐diversity was associated significantly with the receipt of a carbapenem P < 0.001. Domination events by the majority of genera were transient (median duration, 1 sample), whereas the number of domination events by pathogenic genera increased significantly over the course of IC (P = .002). Moreover, patients who lost microbial diversity over the course of IC were significantly more likely to contract a microbiologically documented infection within the 90 days after IC neutrophil recovery (P = .04). CONCLUSIONS The current data present the largest longitudinal analyses to date of oral and stool microbiomes in patients with AML and suggest that microbiome measurements could assist with the mitigation of infectious complications of AML therapy. Cancer 2016;122:2186–96. © 2016 American Cancer Society. Correlations between microbiome composition and infectious outcomes in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy were investigated. The results indicate that longitudinal analyses and measurements of oral and stool microbiomes in patients with AML can assist with risk assessment or mitigation of infectious complications during AML therapy.