Chronic graft-versus-host disease: Current situation and unmet needs - A European position statement

Chronic graft-versus-host disease (cGVHD) remains the leading cause of late morbidity and non-relapse mortality after allogeneic hematopoietic cell transplantation, despite major advances in transplant techniques and supportive care. This European position statement provides a comprehensive and forward-looking synthesis of the evolving biology, epidemiology, diagnosis, and management of cGVHD, while highlighting critical unmet needs that impede progress. cGVHD arises from a complex interplay of immune dysregulation, aberrant tissue repair, and progressive fibrosis, resulting in a heterogeneous clinical spectrum that profoundly impairs quality of life and functional status. Although recent therapeutic innovations-including JAK inhibition, ROCK2 inhibition, and CSF-1R-directed therapies-have expanded options beyond corticosteroids, treatment responses remain variable, and optimal sequencing, biomarkers of activity, and organ-specific strategies are lacking. Persistent challenges in diagnosis, staging reproducibility, integration of patient-reported outcomes, and harmonized clinical trial endpoints further limit clinical and regulatory advancement. The substantial pharmaco-economic burden of cGVHD underscores the urgency of developing more effective, durable, and accessible interventions. This review outlines a collaborative roadmap centered on biomarker-driven precision medicine, harmonized assessment tools, integrated supportive care, and international research networks, aiming to transform cGVHD from a debilitating complication into a predictable, preventable, and ultimately curable condition.