Toward Improving Initial Therapy of Acute Graft Versus Host Disease

Acute graft versus host disease (aGVHD) is a major complication of hematopoietic stem cell transplantation; it results from donor-derived immune response against host tissues and typically involves the liver, skin and the GI tract. The incidence of acute GVHD is declining due to the advances in HLA typing, reduced intensity conditioning and GVHD prophylaxis. However, corticosteroids remain the mainstay frontline treatment of aGVHD for many decades and as the number of allogeneic transplants continues to increase, there remains a large unmet need to improve frontline treatment for aGVHD. In this review, we outline risk factors, epidemiology and pathogenesis of aGVHD. We discuss the evolving risk stratification, beginning from the initial Gluckesberg system to more recent biomarker-based strategies. We summarize the completed trials that underpin current frontline management and outline future directions.