# Current status, challenges, and integration pathways of biomarker classification systems in graft-versus-host disease: a preliminary exploration

## TL;DR

This paper reviews current systems for classifying GVHD biomarkers and proposes a new framework to improve data integration and clinical application.

## Contribution

The paper introduces a three-dimensional classification system for GVHD biomarkers integrating pathophysiology, clinical use, and molecular traits.

## Key findings

- A three-dimensional system for GVHD biomarkers was developed based on pathophysiology, clinical scenarios, and molecular traits.
- Key challenges in biomarker research and application were identified, along with potential integration pathways.
- A systematic review of 139 articles revealed fragmented classification systems limiting clinical translation.

## Abstract

Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation that impairs clinical outcomes. Existing classification systems for GVHD biomarkers remain fragmented, which limits cross-study data integration and clinical translation, creating an urgent need for a systematic classification framework.

In this review, a predefined search strategy was used to systematically evaluate the classification systems of GVHD biomarkers. For the search, a systematic literature retrieval was conducted in the PubMed and Web of Science databases, covering the time range from 2012 to 2025, with keywords including “GVHD,” “biomarkers,” and “classification and summarization.” The inclusion criteria for studies were as follows, focusing on the classification or clinical application of GVHD biomarkers: peer-reviewed original articles, reviews, or multicenter trials, and human subjects or well-validated mouse models. After screening, a total of 139 articles were included in this review.

This review integrates GVHD biomarkers into a three-dimensional system, including pathophysiological mechanisms, clinical application scenarios, and molecular characteristics. It identifies key challenges in biomarker research and application, and proposes feasible integration pathways. This work provides a foundational framework for precision medicine in GVHD management.