Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day+100 survival following haematopoietic stem cell transplantation
Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day+100 survival following haematopoietic stem cell transplantation
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DOI：
10.1111/bjh.14727
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发表时间：
2017-07-01
影响因子：
6.5
通讯作者：
Soiffer, Robert J.
中科院分区：
文献类型：
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作者：
Richardson, Paul G.;Smith, Angela R.;Soiffer, Robert J.
肝静脉闭塞性疾病/肝窦阻塞综合征（VOD/SOS）是造血干细胞移植（HSCT）预处理的一种进行性、潜在致命的并发症。VOD/SOS病理生理级联反应涉及内皮细胞活化和损伤，以及促血栓形成-低纤溶状态。严重VOD/SOS（通常以多器官功能障碍为特征）可能与>80%的死亡率相关。去纤维蛋白多核苷酸在欧盟被批准用于治疗HSCT后的重度肝VOD/SOS，在美国被批准用于治疗HSCT后的伴有肾或肺功能障碍的肝VOD/SOS。以前，去纤维蛋白多核苷酸（25 mg/kg/天，分4次给药，推荐>= 21天）可通过VOD/SOS患者的扩展治疗方案获得。事后检查本研究的数据，以确定VOD/SOS诊断后开始去纤维蛋白多核苷酸的时间是否影响HSCT后第+100天的生存率。在573例患者中，约30%的患者在VOD/SOS诊断当天开始使用去纤维蛋白多核苷酸，> 90%的患者在7天内开始使用。第+100天生存率与诊断后特定天数之前/之后开始治疗之间的关系显示，在接近VOD/SOS诊断时开始治疗时，上级生存率更高，随着时间的推移，早期开始治疗的结局更好，这一趋势具有统计学显著性（P < 0.001）。这些结果表明，开始去纤维蛋白多核苷酸不应该被推迟后诊断VOD/SOS。
Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a progressive, potentially fatal complication of conditioning for haematopoietic stem cell transplant (HSCT). The VOD/SOS pathophysiological cascade involves endothelial-cell activation and damage, and a prothrombotic-hypofibrinolytic state. Severe VOD/SOS (typically characterized by multi-organ dysfunction) may be associated with >80% mortality. Defibrotide is approved for treating severe hepatic VOD/SOS post-HSCT in the European Union, and for hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States. Previously, defibrotide (25 mg/kg/day in 4 divided doses for a recommended >= 21 days) was available through an expanded-access treatment protocol for patients with VOD/SOS. Data from this study were examined post-hoc to determine if the timing of defibrotide initiation post-VOD/SOS diagnosis affected Day +100 survival post-HSCT. Among 573 patients, defibrotide was started on the day of VOD/SOS diagnosis in approximately 30%, and within 7 days in >90%. The relationship between Day +100 survival and treatment initiation before/after specific days post-diagnosis showed superior survival when treatment was initiated closer to VOD/SOS diagnosis with a statistically significant trend over time for better outcomes with earlier treatment initiation (P < 0.001). These results suggest that initiation of defibrotide should not be delayed after diagnosis of VOD/SOS.