Treatment and unmet needs in steroid-refractory acute graft-versus-host disease

Abstract

Acute graft-versus-host disease (aGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (alloHCT) and is a major cause of morbidity and mortality. Systemic steroid therapy is the first-line treatment for aGVHD, although about half of patients will become refractory to treatment. As the number of patients undergoing alloHCT increases, developing safe and effective treatments for aGVHD will become increasingly important, especially for those whose disease becomes refractory to systemic steroid therapy. This paper reviews current treatment options for patients with steroid-refractory aGVHD and discusses data from recently published clinical studies to outline emerging therapeutic strategies.

Fig. 1. Pathophysiology of acute graft-versus-host disease.

During phase I, conditioning chemotherapy or radiation damages tissues and causes release of inflammatory cytokines; during phase II, donor T cells are activated; and in phase III, T cells migrate to target tissues and cause apoptosis. APC antigen-presenting cell, CTL cytotoxic T lymphocyte, IDO indoleamine 2,3-dioxygenase, IFN interferon, IL interleukin, LPS lipopolysaccharide, NK natural killer cell, NOD2 nucleotide-binding oligomerization domain–containing protein 2, TNF tumor necrosis factor, Treg regulatory T cell. From Harris et al. Br J Haematol. 2013;160:288–302. © 2012 Blackwell Publishing Ltd.