Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19
Name
biomolecules-15-01004-v4.pdf
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1.25 MB
Format
Adobe PDF
Checksum (MD5)
a122a93206e9c1fc1878469a755d73af
Author(s)
Richardson, Edward
Mo, Clifton C.
Calabretta, Eleonora
Corrado, Francesco
Kocoglu, Mehmet H.
Baron, Rebecca M.
Connors, Jean Marie
Iacobelli, Massimo
Wei, Lee-Jen
Benjamin, Emily J.
Date Issued
July 14, 2025
Journal
Biomolecules
Publisher
Multidisciplinary Digital Publishing Institute
Citation
Richardson, E.; Mo, C.C.; Calabretta, E.; Corrado, F.; Kocoglu, M.H.; Baron, R.M.; Connors, J.M.; Iacobelli, M.; Wei, L.-J.; Benjamin, E.J.; et al. Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19. Biomolecules 2025, 15, 1004.
Version
Final published version
Abstract
Defibrotide, which is approved for treating hepatic veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), exhibits pleiotropic anti-inflammatory, anti-thrombotic, and fibrinolytic properties, conferring broad endothelial protective effects. Given these mechanisms, defibrotide has potential utility in various conditions involving endothelial injury or activation. In this review we outline the endothelial-protective mechanisms of defibrotide and comprehensively summarize current evidence supporting its applications in hematologic malignancies, including the prevention and treatment of hepatic VOD/SOS, graft-versus-host disease, and transplant-associated thrombotic microangiopathy. Additionally, we discuss its role in mitigating key toxicities linked to chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We also explore emerging evidence on defibrotide’s potential in SARS-CoV-2 infection-associated endotheliopathies, including acute COVID-19 and post-acute sequelae of SARS-CoV-2 infection (“long-COVID”), and the endothelial protective activity of defibrotide in these settings. Finally, we highlight potential future applications of defibrotide in hematologic malignancies and viral infections, emphasizing its multimodal mechanism of action.
MIT Department
Broad Institute of MIT and Harvard
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.3390/biom15071004
