Managing acute graft-versus-host disease after allogeneic stem cell transplantation

INTRODUCTION: Acute graft-versus-host disease (aGVHD) remains a leading cause of morbidity and non-relapse mortality after allogeneic hematopoietic cell transplantation. Despite progress in prophylactic strategies, its management remains challenging: corticosteroids are still the mainstay of first-line care, yet a substantial proportion of patients fail to achieve durable responses, underscoring the need for more effective and less toxic alternatives. AREAS COVERED: This review outlines the current approach to aGVHD, from first-line management to steroid-refractory disease and beyond. It covers corticosteroid optimization, the established role of ruxolitinib in the steroid-refractory setting, and the use of extracorporeal photopheresis in selected patients. Cellular, microbiome-based, cytokine-directed, and regenerative strategies acting on complementary pathogenic mechanisms are also discussed. The literature was identified through a PubMed search using the terms 'acute graft-versus-host disease' and 'treatment,' including publications up to 30 June 2026, supplemented by manual screening of reference lists. EXPERT OPINION: Ruxolitinib has reshaped the management of steroid-refractory aGVHD, although important unmet needs persist. Future progress will depend not only on new agents but on smarter use of existing options: minimizing steroid exposure, refining sequencing, and integrating combinations earlier. Biomarker-guided risk stratification may ultimately support a more individualized approach, improving disease control while limiting toxicity.