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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MDPI AG
2025-07-01
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| Online Access: | https://www.mdpi.com/2218-273X/15/7/1004 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Edward Richardson |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-629ed4361b3d4353b86caaa6e85e5b71 |
| institution | DOAJ |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-629ed4361b3d4353b86caaa6e85e5b712025-08-20T03:08:05ZengMDPI AGBiomolecules2218-273X2025-07-01157100410.3390/biom15071004Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19Edward Richardson0Clifton C. Mo1Eleonora Calabretta2Francesco Corrado3Mehmet H. Kocoglu4Rebecca M. Baron5Jean Marie Connors6Massimo Iacobelli7Lee-Jen Wei8Emily J. Benjamin9Aaron P. Rapoport10Maribel Díaz-Ricart11Antonio José Martínez-Mellado12Carmelo Carlo-Stella13Paul G. Richardson14José M. Moraleda15Department of Medicine, Warren Alpert Medical School at Brown University, Providence, RI 02903, USADepartment of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA 02215, USADepartment of Biomedical Sciences, Humanitas University, 20089 Milan, ItalyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA 02215, USAUniversity of Maryland Greenebaum Comprehensive Cancer Center, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USADivision of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USADivision of Hematology, Brigham and Women’s Hospital, Boston, MA 02115, USATechitra S.r.l., 20123 Milan, ItalyDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USADepartment of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA 02215, USAUniversity of Maryland Greenebaum Comprehensive Cancer Center, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USAHematopathology, Pathology Department, CDB, Hospital Clinic, IDIBAPS, 08036 Barcelona, SpainDepartment of Hematology, University Hospital Virgen de la Arrixaca, IMIB-Pascual Parrilla, University of Murcia, 30120 Murcia, SpainDepartment of Biomedical Sciences, Humanitas University, 20089 Milan, ItalyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA 02215, USADepartment of Medicine, Faculty of Medicine, Institute of Biomedical Research (IMIB-Pascual Parrilla), University of Murcia, 30120 Murcia, SpainDefibrotide, 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.https://www.mdpi.com/2218-273X/15/7/1004CAR T-cell therapybispecific antibodies/bispecific T-cell engagersCOVID-19CRSendotheliitisendotheliopathy |
| spellingShingle | 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 Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19 Biomolecules CAR T-cell therapy bispecific antibodies/bispecific T-cell engagers COVID-19 CRS endotheliitis endotheliopathy |
| title | Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19 |
| title_full | Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19 |
| title_fullStr | Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19 |
| title_full_unstemmed | Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19 |
| title_short | Defibrotide for Protecting Against and Managing Endothelial Injury in Hematologic Malignancies and COVID-19 |
| title_sort | defibrotide for protecting against and managing endothelial injury in hematologic malignancies and covid 19 |
| topic | CAR T-cell therapy bispecific antibodies/bispecific T-cell engagers COVID-19 CRS endotheliitis endotheliopathy |
| url | https://www.mdpi.com/2218-273X/15/7/1004 |
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