Pathogenesis and management of graft-versus-host disease

Allogeneic hematopoietic cell transplantation (HCT) is an important therapeutic option for various malignant and nonmalignant conditions. As allogeneic HCT continues to increase, greater attention is given to improvements in supportive care, infectious prophylaxis, immunosuppressive medications, and DNA-based tissue typing. However, graft versus host disease (GVHD) remains the most frequent and serious complication following allogeneic HCT and limits the broader application of this important therapy. Recent advances in the understanding of the pathogenesis of GVHD have led to new approaches to its management, including using it to preserve the graft versus leukemia effect following allogeneic transplant. This article reviews the important elements in the complex immunologic interactions involving cytokine networks, chemokine gradients, and the direct mediators of cellular cytotoxicity that cause clinical GVHD, and discusses the risk factors and strategies for management of GVHD.