# Evaluating Effects of Age-related Microbiota Modulations in Hematopoietic Stem Cell Transplant Patients

> **NIH NIH R21** · DUKE UNIVERSITY · 2020 · $201,250

## Abstract

Allogeneic hematopoietic stem cell transplant (HCT) has the potential to cure patients with hematologic
malignancies. However, HCT is associated with significant treatment related mortality (TRM) ranging from 20-
30%. (1). TRM is particularly high in patients with advanced age (hazard ratio 1.84, age >60 years vs. <20) and
decreased physical function (hazard ratio 2.94, bottom quartile vs. top quartile). A major cause of TRM is graft-
versus-host disease (GVHD), which affects 40-60% of patients. We hypothesis that age related microbiome
changes will affect the HCT clinical outcomes, and in addition to age other factors such as diet, physical activity
and the care environment can influence the microbiome profiles as well.
 Correlations between GVHD and disruptions in the gut microbiota have been reported in several studies,
though it remains unclear how the microbiota causes or prevents GVHD. While lengthy hospitalizations are
standard for HCT patients, caring for patients in a more normal care environment may preserve the natural
microbiota. We hypothesized that shifting the care environment from the hospital to a more normal environment
like the home can preserve the gut microbiota, thereby decreasing intestinal inflammation and GVHD. We have
successfully piloted home HCT in a phase 1 trial (co-PIs Chao, Sung, clinicaltrials.gov NCT01725022) and have
expanded our pilot into a randomized phase 2 study of home vs. standard care (clinicaltrials.gov NCT02218151,
co-PIs Chao, Sung) funded by NCI 1R01CA203950 (PI Chao, co-I Sung).
 While age cannot be changed, other strategies to overcome the negative effects of aging-related
microbiome changes can be the use of dietary and physical activity interventions. We have started a Phase I/II,
pre- and peri-HCT optimization program (PPOP). PPOP has two pieces: a clinical component (C-PPOP), which
establishes a new standard of care for the pre-HCT evaluation of all Duke HCT patients, and a research
component (R-PPOP), which includes additional assessments and interventions to optimize health and function
including diet and physical activity. In this proposed project we aim to: 1) evaluate the age related microbiome
changes and their implications on HCT outcomes including TRM (primary endpoint), infections, GVHD, and
immune function; 2) evaluate the effects of a dietary and physical activity intervention on the aged microbiome
and implications on HCT outcomes.
 For this study will be able to utilize existing samples from the Duke Hematologic Malignancies
Biorepository. This study can provide new insights into the underlying mechanisms of GVHD in Leukemia and
other malignant diseases. If successful, this study will identify the impact of age related microbiome changes on
HCT outcomes and the immune system, as well as strategies to target the aged microbiome to promote better
outcomes for HCT patients.

## Key facts

- **NIH application ID:** 9980757
- **Project number:** 5R21AG066388-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Nelson J. Chao
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,250
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980757

## Citation

> US National Institutes of Health, RePORTER application 9980757, Evaluating Effects of Age-related Microbiota Modulations in Hematopoietic Stem Cell Transplant Patients (5R21AG066388-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9980757. Licensed CC0.

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