Immunopathology and biology-based treatment of steroid-refractory graft-versus-host disease.

Blood
Tomomi Toubai, John Magenau

Abstract

Acute graft-versus-host disease (GVHD) is 1 of the major life-threating complications after allogeneic cell transplantation. Although steroids remain first-line treatment, roughly one-half of patients will develop steroid-refractory GVHD (SR-GVHD), which portends an extremely poor prognosis. Many agents that have shown encouraging response rates in early phase 1/2 trials for prevention and treatment have been unsuccessful in demonstrating a survival advantage when applied in the setting of SR-GVHD. The discovery of novel treatments has been further complicated by the absence of clinically informative animal models that address what may reflect a distinct pathophysiology. Nonetheless, the combined knowledge of established bone marrow transplantation models and recent human trials in SR-GVHD patients are beginning to illuminate novel mechanisms for inhibiting T-cell signaling and promoting tissue tolerance that provide an increased understanding of the underlying biology of SR-GVHD. Here, we discuss recent findings of newly appreciated cellular and molecular mechanisms and provide novel translational opportunities for advancing the effectiveness of treatment in SR-GVHD.

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Citations

Mar 23, 2021·The Cancer Journal·Norihiro Watanabe, Maksim Mamonkin
Mar 31, 2021·Transplantation and Cellular Therapy·Rohtesh S MehtaAmin Alousi
Aug 29, 2021·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Paul Szabolcs
Jan 23, 2022·American Journal of Hematology·Xiao-Dong MoXiao-Jun Huang

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