Biomarker-driven strategies and challenges in acute graft-versus-host disease clinical trials

Acute graft-versus-host disease (GVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation. Traditional risk stratification based on clinical symptoms provides only modest prognostic accuracy for treatment response and long-term outcomes. Several biomarkers have shown promise in improving predictive and prognostic precision. Biomarker-guided strategies can identify high-risk patients before extensive target organ damage occurs and low-risk patients who may benefit from lower-intensity treatment, thereby reducing GVHD-related organ injury and adverse effects such as infection and disease relapse. These approaches have facilitated more personalized treatment, with some studies reporting reduced infection rates and improved GVHD-related outcomes in appropriately selected populations. Biomarker-driven clinical trial designs represent a promising framework for developing risk-adapted GVHD management strategies; however, continued validation and refinement of biomarker algorithms is essential to optimize patient outcomes.