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, Rapoport Aaron P, Díaz-Ricart Maribel, Martínez-Mellado Antonio José, Carlo-Stella Carmelo, Richardson Paul G, Moraleda José M
Department of Medicine, Warren Alpert Medical School at Brown University, Providence, RI 02903, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA 02215, USA.
Biomolecules. 2025 Jul 14;15(7):1004. doi: 10.3390/biom15071004.
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.
去纤苷已被批准用于治疗肝静脉闭塞病（VOD）/窦性阻塞综合征（SOS），具有多效性的抗炎、抗血栓形成和纤维蛋白溶解特性，具有广泛的内皮保护作用。鉴于这些机制，去纤苷在各种涉及内皮损伤或激活的病症中具有潜在用途。在本综述中，我们概述了去纤苷的内皮保护机制，并全面总结了支持其在血液系统恶性肿瘤中应用的现有证据，包括肝VOD/SOS的预防和治疗、移植物抗宿主病以及移植相关的血栓性微血管病。此外，我们讨论了其在减轻与嵌合抗原受体（CAR）T细胞疗法和双特异性抗体相关的关键毒性方面的作用，如细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）。我们还探讨了关于去纤苷在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染相关内皮病变中的潜力的新证据，包括急性冠状病毒病2019（COVID-19）和SARS-CoV-2感染的急性后遗症（“长新冠”），以及去纤苷在这些情况下的内皮保护活性。最后，我们强调了去纤苷在血液系统恶性肿瘤和病毒感染中的潜在未来应用，强调其多模式作用机制。
