Accès ouvert déclaré 2021 preprint

Randomized controlled trial of gut decontamination in pediatric patients undergoing allogeneic hematopoietic cell transplantation

Christopher J. Severyn, Benjamin A. Siranosian, Sandra Tian-Jiao Kong, Ángel Moreno, Michelle M. Li, Nan Chen, Christine Duncan, Steven P. Margossian, Leslie Lehmann, Shan Sun, Tessa M. Andermann, Olga Birbrayer, Sophie Silverstein, Soomin Kim, Niaz Banaei, Jerome Ritz, Anthony A. Fodor, Wendy B. London, Ami Siddharth Bhatt, Jennifer Whangbo

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Le résumé fourni par la source

ABSTRACT Background Gut decontamination (GD) can decrease the incidence and severity of acute graft- versus-host-disease (aGVHD) in murine models of allogeneic hematopoietic cell transplantation (HCT). Several HCT centers standardly practice GD with different antibiotic regimens. In this pilot study, we examined the impact of GD on the gut microbiome composition and incidence of aGVHD in HCT patients. Methods We randomized 20 pediatric patients undergoing allogeneic HCT to receive (GD) or not receive (no-GD) oral vancomycin-polymyxin B from day -5 through neutrophil engraftment. We evaluated shotgun metagenomic sequencing of serial stool samples to compare the composition and diversity of the gut microbiome between study arms. We assessed clinical outcomes in the 2 arms and performed strain-specific analyses of pathogens that caused bloodstream infections (BSI). Results The two arms did not differ in Shannon diversity of the gut microbiota at two weeks post- HCT (Genus, p= 0.8; Species, p= 0.44) or aGVHD incidence ( p =0.58). Immune reconstitution of T- cell subsets was similar, but absolute CD19+ B-cell counts were higher in the GD arm at 12 months post-HCT ( p =0.02). Five patients in the no-GD arm had eight BSI episodes vs one episode in the GD arm ( p =0.09). The BSI-causing pathogens were traceable to the gut in seven of eight BSI episodes in the no-GD arm, including the genus Staphylococcus . Conclusions While GD did not differentially impact Shannon diversity or clinical outcomes, our findings suggest that GD may protect against gut-derived BSI in HCT patients by decreasing the prevalence or abundance of gut microbial pathogens. Key points: – In this phase 2 randomized study of gut decontamination (GD) in 20 pediatric HCT patients, neither two-week post-HCT Shannon diversity of the gut microbiome nor incidence of aGVHD differ between the GD and no-GD arms. – All bloodstream infections (BSIs) caused by pathogens traceable to the gut either temporally or via strain-specific analysis (concomitant gut colonization) occurred in patients in the no-GD arm; this suggests that GD with vancomycin-polymyxin B may decrease the incidence of gut-derived BSI in allo-HCT patients. – In contrast to prior studies, we find that non-mucosal barrier injury (MBI) pathogens, such as Staphylococcus aureus, can be found in the gut microbiome of HCT patients.

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Le contrôle bibliographique ouvert

DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.

Titre Crossref: Randomized controlled trial of gut decontamination in pediatric patients undergoing allogeneic hematopoietic cell transplantation
Date Crossref: 17/12/2021
Éditeur: openRxiv
Type: posted-content

Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.

Où se fait cette recherche

Stanford University Department of Pediatrics pays non établi dans la notice
Université ou école supérieure
Palo Alto University pays non établi dans la notice
Université ou école supérieure
Harvard University pays non établi dans la notice
Université ou école supérieure
Dana-Farber/Boston Children's Cancer and Blood Disorders Center pays non établi dans la notice
Établissement de santé
University of North Carolina at Charlotte Department of Bioinformatics and Genomics pays non établi dans la notice
Université ou école supérieure
University of North Carolina at Chapel Hill Department of Medicine pays non établi dans la notice
Université ou école supérieure
Dana-Farber Cancer Institute pays non établi dans la notice
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Department of Biomedical Informatics pays non établi dans la notice
Institution
Dana-Farber/Boston Children’s Cancer & Blood Disorders Center pays non établi dans la notice
Institution
Harvard Medical School pays non établi dans la notice
Institution

Department of Pediatrics — Stanford University, Palo Alto University et Harvard University, avec 7 autres affiliations.

Une affiliation ne permet pas de déduire la nationalité d’un auteur.

Les sujets associés

Gut microbiota and healthNeutropenia and Cancer InfectionsClostridium difficile and Clostridium perfringens research

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