In a study of children who received allogeneic hematopoietic stem cell transplantation (allo-HCT), researchers found associations between intestinal microbiota and infections or acute graft vs host disease (aGVHD). The researchers reported their findings in The Journal of Infectious Diseases.
“We found that the intestinal microbiota in pediatric patients undergoing allo-HCT are highly variable but that compositional signatures predict both infectious and aGVHD outcomes,” the researchers wrote in their report.
The study was a prospective, observational analysis that involved evaluation of stool samples obtained from patients 18 years of age or younger. Patients had been treated with allo-HCT at St. Jude Children’s Research Hospital in Memphis, Tennessee, during the period of 2016 through 2019. Samples were collected prior to conditioning (baseline), and during the time of neutrophil recovery, and they were evaluated using sequencing of 16S ribosomal RNA.
The study had a primary outcome of the number of microbiologically defined infections, with secondary outcomes of aGVHD, bacteremia, viral enterocolitis, and Clostridioides difficile infection (CDI).
There were 74 children included in this study, and they had a median age of 8.35 years (interquartile range [IQR], 4.16-13.74). Patients had a median follow-up time of 12.13 months (IQR, 8.12-12.49). Acute myeloid leukemia was the diagnosis present in 59.5% of the patients. There were 72 children who had samples available at baseline and 64 with samples available at the time of neutrophil recovery.
Infection outcomes included viral enterocolitis in 47.3% of patients, bacteremia in 32.4% of patients, CDI in 35.1% of patients, and others. Grade 1 or 2 aGVHD was reported in 21% of patients, while aGVHD of grade 3 or 4 was reported in 17.5%.
Overall, the researchers found that indicators of microbiome disruption often seen in adult patients were not prominent in the children of this study after allo-HCT, nor were they predictive of outcomes.
However, the researchers did find distinct signatures among microbiota that appeared linked to either aGVHD or infection risks. For example, among patients in their first year after allo-HCT, a certain ratio of strict to facultative anaerobes present at baseline was predictive of a risk of bacteremia (hazard ratio [HR], 3.89; 95% CI, 2.10-7.21). Also, in the first year after allo-HCT, a particular ratio of oral to gut anaerobes present at the time of neutrophil recovery appeared predictive of both a risk of viral enterocolitis (HR, 1.96; 95% CI, 1.38-2.79) and bacterial infections (HR, 1.81; 95% CI, 1.30-2.52) during this period.
“These findings that specific (and many unheralded) bacteria could predict infection and transplant complications in this pediatric cohort differs from what has been seen previously in adult cohorts,” the researchers wrote in their report.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.
Margolis EB, Alfaro GM, Sun Y, et al. Microbiota predict infections and acute graft-versus-host disease after pediatric allogeneic hematopoietic stem cell transplantation. J Infect Dis. Accepted manuscript. Published online May 30, 2023. doi:10.1093/infdis/jiad190