Endothelial injury and dysfunction with emerging immunotherapies in multiple myeloma, the impact of COVID-19, and endothelial protection with a focus on the evolving role of defibrotide

IF 6.9 2区 医学 Q1 HEMATOLOGY Blood Reviews Pub Date : 2024-06-03 DOI:10.1016/j.blre.2024.101218
Clifton C. Mo , Edward Richardson , Eleonora Calabretta , Francesco Corrado , Mehmet H. Kocoglu , Rebecca M. Baron , Jean Marie Connors , Massimo Iacobelli , Lee-Jen Wei , Aaron P. Rapoport , Maribel Díaz-Ricart , José M. Moraleda , Carmelo Carlo-Stella , Paul G. Richardson
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引用次数: 0

Abstract

Patients with multiple myeloma (MM) were among the groups impacted more severely by the COVID-19 pandemic, with higher rates of severe disease and COVID-19-related mortality. MM and COVID-19, plus post-acute sequelae of SARS-CoV-2 infection, are associated with endothelial dysfunction and injury, with overlapping inflammatory pathways and coagulopathies. Existing treatment options for MM, notably high-dose therapy with autologous stem cell transplantation and novel chimeric antigen receptor (CAR) T-cell therapies and bispecific T-cell engaging antibodies, are also associated with endothelial cell injury and mechanism-related toxicities. These pathologies include cytokine release syndrome (CRS) and neurotoxicity that may be exacerbated by underlying endotheliopathies. In the context of these overlapping risks, prophylaxis and treatment approaches mitigating the inflammatory and pro-coagulant effects of endothelial injury are important considerations for patient management, including cytokine receptor antagonists, thromboprophylaxis with low-molecular-weight heparin and direct oral anticoagulants, and direct endothelial protection with defibrotide in the appropriate clinical settings.

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多发性骨髓瘤新兴免疫疗法导致的内皮损伤和功能障碍、COVID-19 的影响以及内皮保护(重点关注去纤维化药物不断演变的作用
多发性骨髓瘤(MM)患者是受 COVID-19 大流行影响较严重的群体之一,他们的重症率和 COVID-19 相关死亡率都较高。MM和COVID-19以及SARS-CoV-2感染的急性后遗症都与内皮功能障碍和损伤有关,并伴有重叠的炎症途径和凝血病。MM的现有治疗方案,特别是自体干细胞移植的大剂量疗法、新型嵌合抗原受体(CAR)T细胞疗法和双特异性T细胞参与抗体,也与内皮细胞损伤和机制相关的毒性有关。这些病理现象包括细胞因子释放综合征(CRS)和神经毒性,可能会因潜在的内皮病变而加重。在这些重叠风险的背景下,减轻内皮损伤的炎症和促凝血效应的预防和治疗方法是患者管理的重要考虑因素,包括细胞因子受体拮抗剂、低分子量肝素和直接口服抗凝剂的血栓预防以及在适当的临床环境中使用去纤肽直接保护内皮。
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来源期刊
Blood Reviews
Blood Reviews 医学-血液学
CiteScore
13.80
自引率
1.40%
发文量
78
期刊介绍: Blood Reviews, a highly regarded international journal, serves as a vital information hub, offering comprehensive evaluations of clinical practices and research insights from esteemed experts. Specially commissioned, peer-reviewed articles authored by leading researchers and practitioners ensure extensive global coverage across all sub-specialties of hematology.
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