Pathophysiology, prevention, and treatment of acute graft-versus-host disease

Correspondence: Joseph P Uberti Department of Oncology, Blood and Marrow Stem Cell Transplant Program, Barbara Ann Karmanos Cancer institute, wayne State University School of Medicine, Detroit, Mi 48201, USA Tel +1 313 576 8760 Fax +1 313 576 8766 email ubertij@karmanos.org Abstract: Acute graft-versus-host disease (aGVHD) is an immunologically mediated inflammatory reaction, which continues to be a major cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplant. Although the occurrence and severity of this disease may be devastating, there is a proven immunologically mediated antitumor activity that accompanies the disease process, which has a beneficial effect on outcome. Animal models of graft-versus-host disease (GVHD) have given us a conceptual model that has allowed a better understanding of the pathophysiology and offers a framework for understanding the complex interactions between antigen-presenting cells, donor T-cells, and cytokines in the development of aGVHD. It has also given us a model that allows testing of various strategies for prevention and treatment. New, innovative approaches for treatment and prevention of aGVHD including better donor selection with the use of sophisticated human leukocyte antigen typing, use of T-cell depletion, reduced-intensity transplant regimens, and improved pharmacologic immunosuppression have improved outcomes by decreasing the incidence and severity of aGVHD. However, the limitation of these strategies is that effective treatment and prevention of aGVHD is often accompanied by a concomitant rise in relapses, graft failure and infections, and ultimately no improvement in overall survival. Investigators are working on understanding the difference between GVHD and graft versus tumor effect, as this would be the key in improving outcomes for our patients. In this review, we will discuss the pathophysiology of aGVHD along with the preventative and treatment strategies.