TY - JOUR
T1 - Gut microbiome signatures are predictive of infectious risk following induction therapy for acute myeloid leukemia
AU - Galloway-Peña, Jessica R.
AU - Shi, Yushu
AU - Peterson, Christine B.
AU - Sahasrabhojane, Pranoti
AU - Gopalakrishnan, Vancheswaran
AU - Brumlow, Chelcy E.
AU - Daver, Naval G.
AU - Alfayez, Mansour
AU - Boddu, Prajwal C.
AU - Khan, Md Abdul Wadud
AU - Wargo, Jennifer A.
AU - Do, Kim Anh
AU - Jenq, Robert R.
AU - Kontoyiannis, Dimitrios P.
AU - Shelburne, Samuel A.
N1 - Funding Information:
This work was supported by the MD Anderson Cancer Center Knowledge Gap funding to D. P. K. and S. A. S.; the MD Anderson Cancer Center Multidisciplinary Research Program funding to D. P. K., S. A. S., and J. A. W.; the MD Anderson Odyssey Fellowship Program to J. G. P.; the College Football Playoff Foundation Foundation to J. G. P.; the National Institute of Allergy and Infectious Disease (1 K01 AI143881-01 to J. G. P.); the National Cancer Institute (Cancer Center Support grant P30CA016672 to C. B. P. and 1 R01 CA219896-01A1 to J. A. W.); the US-Israel Binational Science Foundation (201332 to J. A. W.); the Kennedy Memorial Foundation (0727030 to J. A. W.); the American Association for Cancer Research Stand Up To Cancer (SU2C-AACR-IRG-19-17 to J. A. W.); the Department of Defense (W81XWH-16-1-0121 to J. A. W.), the Andrew Sabin Family Fellows Program to J. A. W.; and the Texas 4000 Distinguished Professorship for Cancer Research to D. P. K.
Publisher Copyright:
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Background. The majority of studies that provide insights into the influence of the microbiome on the health of hematologic malignancy patients have concentrated on the transplant setting. Here, we sought to assess the predictive capacity of the gastrointestinal microbiome and its relationship to infectious outcomes 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 (hazard ratio [HR], 0.36; 95% confidence interval [CI],.18-.74) and higher relative abundance of Porphyromonadaceae (HR, 0.36; 95% CI,.18-.73) were associated with increased probability of remaining infection-free during neutropenia. A baseline stool Shannon diversity cutoff of <2 had optimal operating characteristics for predicting infectious complications during neutropenia. Although 56 patients received therapy >72 hours with a carbapenem, none of the patients had an infection with an extended spectrum ß-lactamase-producing organism. Patients who received carbapenems for >72 hours had significantly lower a-diversity at neutrophil recovery (P =.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 in AML patients.
AB - Background. The majority of studies that provide insights into the influence of the microbiome on the health of hematologic malignancy patients have concentrated on the transplant setting. Here, we sought to assess the predictive capacity of the gastrointestinal microbiome and its relationship to infectious outcomes 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 (hazard ratio [HR], 0.36; 95% confidence interval [CI],.18-.74) and higher relative abundance of Porphyromonadaceae (HR, 0.36; 95% CI,.18-.73) were associated with increased probability of remaining infection-free during neutropenia. A baseline stool Shannon diversity cutoff of <2 had optimal operating characteristics for predicting infectious complications during neutropenia. Although 56 patients received therapy >72 hours with a carbapenem, none of the patients had an infection with an extended spectrum ß-lactamase-producing organism. Patients who received carbapenems for >72 hours had significantly lower a-diversity at neutrophil recovery (P =.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 in AML patients.
KW - Acute myeloid leukemia
KW - Carbapenem
KW - Induction chemotherapy
KW - Microbiome
KW - Shannon diversity
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U2 - 10.1093/cid/ciz777
DO - 10.1093/cid/ciz777
M3 - Article
C2 - 31436833
AN - SCOPUS:85091779547
SN - 1058-4838
VL - 71
SP - 63
EP - 71
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 1
ER -