# Biologic correlatives of chronic GVHD onset

> **NIH NIH U01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $300,605

## Abstract

PROJECT SUMMARY
Allogeneic hematopoietic cell transplantation (HCT) can cure many hematologic cancers and other life-
threatening hematologic diseases, but 20-50% of survivors develop chronic graft-versus-host disease
(cGVHD), the leading cause of morbidity and mortality in transplant survivors. In cGVHD, the donor's immune
cells attack the patient setting up a cascade of events resulting in a pleomorphic multi-organ syndrome
reminiscent of autoimmune diseases such as systemic sclerosis, systemic lupus erythematosus, Sjogren's
syndrome, and lichen planus. Chronic GVHD is associated with poor quality of life, impaired functional status,
and need for prolonged treatment with potent immunosuppressive agents. There are many competing
hypotheses about the etiology of human cGVHD with data supporting involvement of T and B cells,
macrophages, dendritic cells, fibroblasts and endothelial cells. Cytokines, chemokines and other proteins have
been implicated. To our knowledge, the microbiome has not been investigated in cGVHD patients. This project
will address key gaps in our understanding of human cGVHD development: what are the early events that
occur in the skin, eyes, mouth, and blood before cGVHD clinical onset? Do early changes in local tissues
mirror changes in the rest of the body, and do they reflect the pathophysiology of cGVHD? Can we detect
subclinical cGVHD using new testing strategies, potentially allowing the opportunity for targeted pre-emptive
treatment? To address these questions, we will enroll 100 evaluable patients (80 at Fred Hutchinson, 20 at the
National Cancer Institute) in a prospective, longitudinal study involving intensive bimonthly assessments.
Entitled the “CATCH” study (Close Assessment and Testing for Chronic GVHD), this unique cohort will allow
us to “watch” cGVHD as it develops in humans. No other situation in medicine except solid organ
transplantation provides a similar window into the evolution of an alloimmune response, and findings could be
relevant to many other auto- and alloimmune phenomenon. Participants will be studied before transplant, then
at bimonthly intervals through the first post-transplant year starting at month 3. Assessments include physical
exams, symptom measurement, and sampling of blood, conjunctival washings, saliva, and feces. Participants
will undergo skin and oral biopsies at 2-3 timepoints and also have optical coherence tomography and other
specialized imaging of the skin, eyes, and mouth every other month. Biologic analyses of cytokines,
chemokines, microbiome and cellular subsets will be performed on informative samples to test prior
observations in the murine and human systems and to generate new hypotheses. Completion of this project
will advance our understanding of the biologic underpinnings of human cGVHD and guide therapeutic
approaches based on a comprehensive understanding of systemic and tissue-specific pathophysiology, in
order to decrease the morbidity and mortality of this com...

## Key facts

- **NIH application ID:** 9970455
- **Project number:** 5U01CA236229-02
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** STEPHANIE J LEE
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $300,605
- **Award type:** 5
- **Project period:** 2019-07-02 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970455

## Citation

> US National Institutes of Health, RePORTER application 9970455, Biologic correlatives of chronic GVHD onset (5U01CA236229-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9970455. Licensed CC0.

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