# Probiotics for Prevention of Acute Graft-vs-Host Disease in Children with Cancer

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $1

## Abstract

Project Summary
Despite prophylactic immune suppression, clinically significant (Grade II–IV) acute graft-versus-host disease
(aGvHD) afflicts up to 45% of pediatric patients receiving allogeneic hematopoietic cell transplantation
(alloHCT). As aGvHD is responsible for nearly 20% of deaths following alloHCT, the need for better prevention
and therapy for aGvHD is readily apparent. Involvement of the gastrointestinal (GI) tract in the pathogenesis
of aGvHD has been substantiated by the translation of pre-clinical and clinical studies. Emerging evidence
suggests that perturbations in the microbiota diversity result in aberrant systemic immune response as well as
pathogen colonization and mucosal invasion, fostering the development of GvHD. Pre-clinical studies also
suggest that replenishing commensals like Lactobacillus prior to HCT substantially decrease GvHD severity
and intestinal insult. Our pilot data suggest that probiotics are safe to administer prior to and during children
and adolescents undergoing HCT (IND#108,977). This proposal is a double-blind, randomized, multi-center
intervention trial to evaluate the specific effect of probiotics in preventing GI aGvHD and more generally the
effects on overall GvHD severity. The proposal is an approved concept of Children’s Oncology Group’s (COG),
a NCI National Clinical Trial Network group. The study will be conducted through COG using its clinical
research infrastructure. Correlative laboratory studies (plasma and stool analysis) will be performed in order to
elucidate the mechanisms of action of probiotic therapy. The probiotic, Lactobacillus plantarum (LBP), or
placebo will be administered to 384 evaluable children and adolescents undergoing alloHCT for hematologic
malignancy beginning with the initiation of conditioning through Day 56. We hypothesize that maintaining
epithelial cell integrity through the administration of probiotic therapy will lead to restoring microbial diversity,
which will preserve immune tolerance and prevent aGvHD. The primary study aim is to determine efficacy of
orally-administered LBP in preventing the development of GI aGvHD in children and adolescents undergoing
alloHCT for the treatment of cancer. Secondary study aims are: (1) To determine whether orally-administered
LBP decreases the incidence of Grade II–IV aGvHD following alloHCT; (2) To determine whether LBP
administration maintains intestinal integrity as measured by mean plasma citrulline levels and reduction in
mucosal barrier injury (MBI) bacteremia; (3a) To measure the effects of LBP on the intestinal flora phylogenetic
composition during and after alloHCT using 16S rRNA gene deep sequencing; (3b) To measure effects of LBP
on intestinal flora function during and after alloHCT using metagenomic and metabolite profiling; and (4) To
measure proposed immunomodulatory effects of LBP in mean plasma levels of alloreactive-induced
inflammatory cytokines (IL-2, IL-6, IL-12p70, IFNγ, and TNFα) in patients receiving ...

## Key facts

- **NIH application ID:** 10474290
- **Project number:** 5R01CA201788-07
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Monica Bhatia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1
- **Award type:** 5
- **Project period:** 2016-09-06 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474290

## Citation

> US National Institutes of Health, RePORTER application 10474290, Probiotics for Prevention of Acute Graft-vs-Host Disease in Children with Cancer (5R01CA201788-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10474290. Licensed CC0.

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