# Hydrogen in Patients With Corticosteroid-Refractory/Dependent Chronic Graft-Versus-Host-Disease: A Single-Arm, Multicenter, Open-Label, Phase 2 Trial.
> コルチコステロイド抵抗性・依存性慢性移植片対宿主病患者における水素の効果：単群・多施設・非盲検・第2相試験


## Abstract

Chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic stem cell transplantation remains a major cause of late non-relapse mortality, with no established approach for corticosteroid-refractory or corticosteroid-dependent cases. This prospective, open-label, multicenter phase 2 study enrolled 24 patients (median age 27 years) who received hydrogen-rich water orally at 4 ml/kg three times daily. Organ responses were evaluated every 3 months across skin, mouth, gastrointestinal tract, liver, eyes, lungs, and joints. An objective response was observed in 18 of 24 patients (75%; 95% CI: 55.1–88%). The estimated 4-year overall survival rate reached 74.7% (95% CI: 54.9–94.5%), and the response group demonstrated significantly superior 4-year survival compared with non-responders (86.6% vs. 0%; p=0.000132). No significant adverse effects were associated with long-term hydrogen-rich water administration. The trial was registered at ClinicalTrials.gov (NCT02918188).

### Mechanism

Hydrogen's selective scavenging of reactive oxygen species and its anti-inflammatory properties are proposed to reduce immune-mediated tissue damage characteristic of cGVHD.

## Bibliographic

- **Authors**: Qian L, Liu M, Shen J, Cen J, Zhao D
- **Journal**: Front Immunol
- **Year**: 2020
- **PMID**: [33324415](https://pubmed.ncbi.nlm.nih.gov/33324415/)
- **DOI**: [10.3389/fimmu.2020.598359](https://doi.org/10.3389/fimmu.2020.598359)
- **PMC**: [PMC7724019](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724019/)
- **Study type**: human observational study
- **Delivery route**: hydrogen-rich water
- **Effect reported**: positive

## Delivery context

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

Hydrogen-rich water is a low-risk delivery route, but the achievable systemic hydrogen dose is bounded. For clinical applications, inhalation is the most efficient route; inhalation, however, carries explosion risk, and concentration matters (empirical LFL of 10% applies to inhalation environments; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 33324415. https://h2-papers.org/en/papers/33324415
> **Source**: PubMed PMID [33324415](https://pubmed.ncbi.nlm.nih.gov/33324415/)