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


Journal

Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509

Informations de publication

Date de publication:
23 07 2020
Historique:
received: 05 11 2019
accepted: 24 01 2020
pubmed: 12 6 2020
medline: 26 2 2021
entrez: 12 6 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 32526035
pii: S0006-4971(20)61862-6
doi: 10.1182/blood.2019000953
pmc: PMC7378454
doi:

Substances chimiques

Steroids 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

429-440

Subventions

Organisme : NIAID NIH HHS
ID : K23 AI123595
Pays : United States

Informations de copyright

© 2020 by The American Society of Hematology.

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Auteurs

Tomomi Toubai (T)

Division of Hematology and Cell Therapy, Department of Internal Medicine III, Faculty of Medicine, Yamagata University, Yamagata, Japan; and.

John Magenau (J)

Division of Hematology and Oncology, Department of Internal Medicine, University Michigan Medical School, Ann Arbor, MI.

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