Gut bacteria diversity affects survival among children who undergo stem cell transplant
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- Children with high-diversity gut microbiota prior to HSCT achieved better outcomes.
- Those with diverse gut microbiota before HSCT also had fewer complications, including severe acute GVHD.
Younger patients with diverse gut microbiota prior to allogeneic hematopoietic stem cell transplantation had a significantly lower risk for death following the procedure than those with low diversity, according to study results.
Patients with diverse gut microbiota before HSCT also experienced fewer complications, including high-grade acute graft-versus-host disease, data published in Blood showed.
“The decrease in the diversity of the composition of gut microbiota before allogeneic hematopoietic stem cell transplantation strongly correlates with the survival of children receiving transplantation for hematologic and nononcologic diseases,” Riccardo Masetti, MD, PhD, assistant professor in the department of medicine and surgery at University of Bologna, Italy, told Healio.
The finding suggests interventions to improve microbial diversity prior to transplantation may help more children survive, Masetti added.
Background
Several factors can disrupt a patient’s gut microbiota during allogeneic HSCT process, Masetti said.
“We wanted to study the role of gut microbiota in influencing the clinical outcomes of pediatric patients undergoing hematopoietic stem cell transplantation,” he told Healio. “Many important studies addressed this topic in the adult setting but little evidence is available in the pediatric field.”
Methodology
Masetti and colleagues conducted a retrospective cohort study to determine whether preprocedural gut microbiota composition affected OS among younger patients undergoing allogeneic HSCT for a hematologic malignancy or other nonmalignant disease.
Investigators used stool samples from 90 patients aged 18 years or younger. Samples had been collected as part of previously published studies conducted at five centers in Italy and Poland.
Investigators analyzed stool collected before and after neutrophil engraftment, resulting in 180 total samples.
Researchers used 16S rRNA amplicon sequencing to profile each patient’s gut microbiota and estimate its diversity. They then stratified patients into separate groups based on microbiota diversity before HSCT and at the time of neutrophil engraftment.
OS served as the study’s primary endpoint. Secondary endpoints included RFS and incidence of acute GVHD.
Key findings
Results showed significantly lower risk for death among patients who had higher-diversity gut microbiomes before HSCT (HR = 0.29; 95% CI, 0.11-0.8).
This association persisted after multivariate analysis adjusted for age, graft source, donor type, conditioning type, center and disease type (HR = 0.26; 95% CI, 0.09-0.75).
A higher percentage of patients with high-diversity gut microbiome prior to HSCT remained alive at 52 months (88.9 ± 5.7 vs. 62.7± 8.2; P = .011). They also appeared less likely to develop grade 2 to grade 4 acute GVHD (20 ± 6 vs. 44.4 ± 7.4; P = .017), or grade 3 to grade 4 acute GVHD (2.2 ± 2.2 vs. 20 ± 6; P = .007 ).
A numerically higher percentage of patients with high-diversity gut microbiomes before HSCT remained relapse free at 52 months, but this difference did not reach statistical significance (80 ± 6 vs. 55.4 ± 10.8).
Clinical implications
This study represents the largest case series examining the gut microbiota composition of pediatric patients undergoing HSCT, Masetti said.
“These results can represent an important starting point for planning potential interventions modulating the gut microbiota diversity before hematopoietic stem cell transplantation, thus significantly impacting clinical practice,” he told Healio. “Strategies of antibiotic sparing, diet, enteral nutrition and fecal microbiota transplantation are some of the possible interventions aimed at modulating the composition of gut microbiota before hematopoietic stem cell transplantation.”
For more information:
Riccardo Masetti, MD, PhD, can be reached at riccardo.masetti5@unibo.it.
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Masetti R, et al. Blood. 2023;doi:10.1182/blood.2023020026.
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