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

Blood. 2020 Jul 23;136(4):429-440. doi: 10.1182/blood.2019000953.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Graft vs Host Disease* / etiology
  • Graft vs Host Disease* / immunology
  • Graft vs Host Disease* / pathology
  • Graft vs Host Disease* / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Steroids / therapeutic use
  • Transplantation Tolerance*
  • Transplantation, Homologous


  • Steroids