Jerome Lipper Multiple Myeloma Center, Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Novel Health Strategies, Bethesda, MD, USA.
Bone Marrow Transplant. 2019 Dec;54(12):1951-1962. doi: 10.1038/s41409-019-0474-8. Epub 2019 Feb 25.
Veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT) conditioning or high-dose nontransplant chemotherapy. VOD/SOS with multi-organ dysfunction (MOD) is associated with a mortality rate of > 80%. Defibrotide (25 mg/kg/day) is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post HSCT in the United States and to treat severe hepatic VOD/SOS in patients > 1 month of age in the European Union. A random effects model was used for pooling data from 17 systematically chosen defibrotide studies. For patients in these reports (n = 2598), and those in the subset of 10 reports of patients treated with ~ 25 mg/kg/day (n = 1691), estimated Day + 100 survival rates were 54% and 56%, respectively. Among those patients treated with ~ 25 mg/kg/day, estimated Day + 100 survival was 44% among patients with MOD and 71% in patients without MOD; survival was 41% and 70%, respectively, for the population of patients receiving any dose of defibrotide. Safety results were not pooled owing to differences in reporting methodology but were generally consistent with the known tolerability profile of defibrotide. This analysis provides the largest assessment of survival in patients treated with defibrotide for VOD/SOS with or without MOD.
静脉闭塞性疾病(VOD),也称窦状隙阻塞综合征(SOS),是造血干细胞移植(HSCT)预处理或大剂量非移植化疗的一种潜在致命并发症。伴有多器官功能障碍(MOD)的 VOD/SOS 相关死亡率>80%。美国批准将 25mg/kg/天的地夫可特用于治疗 HSCT 后伴有肾功能或肺功能障碍的肝 VOD/SOS,以及治疗年龄>1 个月的患者的严重肝 VOD/SOS。采用随机效应模型对 17 项系统性地夫可特研究的数据进行汇总。根据这些报告中的患者(n=2598)和接受25mg/kg/天治疗的 10 项报告中患者的亚组(n=1691),估计第+100 天的生存率分别为 54%和 56%。在接受25mg/kg/天治疗的患者中,MOD 患者的估计第+100 天生存率为 44%,无 MOD 患者为 71%;接受任何剂量地夫可特治疗的患者的生存率分别为 41%和 70%。由于报告方法存在差异,安全性结果未进行汇总,但总体上与地夫可特已知的耐受性特征一致。这项分析提供了接受地夫可特治疗的伴有或不伴有 MOD 的 VOD/SOS 患者的最大生存评估。