Emerging strategies for the prevention and management of chronic graft-versus-host disease

Chronic graft-versus-host disease remains a major cause of late morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Conventional prevention and management strategies, heavily reliant on prolonged immunosuppression, are limited by suboptimal efficacy, substantial toxicity, and a failure to address disease heterogeneity.

This review synthesizes recent advances in the biological understanding of cGVHD, particularly the immune dysregulation and fibrotic progression that underpin its diverse clinical manifestations. We discuss a paradigm shift from uniform immunosuppression toward a structured framework encompassing four sequential phases: comprehensive assessment, risk-adapted prevention, mechanism-driven treatment, and holistic long-term survivorship care. Key innovations highlighted include the use of predictive biomarkers for early intervention, the use of steroid-sparing targeted therapies (such as JAK/ROCK2 inhibitors), and the integration of patient-reported outcomes and functional measures into routine evaluation.

The field is poised for transformative change. We advocate for the routine implementation of risk-stratified prevention, preemptive antifibrotic strategies, and organ-specific multidisciplinary management. Crucially, therapeutic success should be redefined around patient-centered goals: safe steroid discontinuation, symptom control, functional recovery, and preserved quality of life. Embedding lifestyle support and longitudinal follow-up into standard care is essential to reduce the overall burden of cGVHD and improve long-term survival.