Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19

Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19

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 poten...

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Main Authors: Edward Richardson, Clifton C. Mo, Eleonora Calabretta, Francesco Corrado, Mehmet H. Kocoglu, Rebecca M. Baron, Jean Marie Connors, Massimo Iacobelli, Lee-Jen Wei, Emily J. Benjamin, Aaron P. Rapoport, Maribel Díaz-Ricart, Antonio José Martínez-Mellado, Carmelo Carlo-Stella, Paul G. Richardson, José M. Moraleda
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Biomolecules
Subjects:
CAR T-cell therapy
bispecific antibodies/bispecific T-cell engagers
COVID-19
CRS
endotheliitis
endotheliopathy
Online Access:https://www.mdpi.com/2218-273X/15/7/1004
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Summary: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.
ISSN:2218-273X

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