Treatment of severe veno-occlusive disease with defibrotide: compassionate use results in response without significant toxicity in a high-risk population.
Treatment of severe veno-occlusive disease with defibrotide: compassionate use results in response without significant toxicity in a high-risk population.
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DOI：
10.1182/blood.v92.3.737
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发表时间：
1998-08
期刊：
影响因子：
20.3
通讯作者：
P. Richardson;A. Elias;A. Krishnan;C. Wheeler;R. Nath;D. Hoppensteadt;Nancy M. Kinchla;D. Neuberg;E. Waller;J. Antin;R. Soiffer;J. Vredenburgh;M. Lill;A. Woolfrey;S. Bearman;M. Iacobelli;J. Fareed;E. Guinan
中科院分区：
文献类型：
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作者：
P. Richardson;A. Elias;A. Krishnan;C. Wheeler;R. Nath;D. Hoppensteadt;Nancy M. Kinchla;D. Neuberg;E. Waller;J. Antin;R. Soiffer;J. Vredenburgh;M. Lill;A. Woolfrey;S. Bearman;M. Iacobelli;J. Fareed;E. Guinan
肝静脉闭塞性疾病（VOD）是干细胞移植（SCT）最常见的方案相关毒性。尽管积极的治疗，包括组织纤溶酶原激活剂（t-PA）和肝素的组合，严重的VOD几乎是一致致命的。去纤肽（DF）是一种多脱氧核糖核苷酸，在几种血管疾病中具有活性，与t-PA和肝素不同，不产生全身抗凝作用。19例SCT后发生严重VOD的患者在同情使用的基础上接受DF治疗。患者有临床确定的VOD，并符合预测进展和死亡的风险标准。在DF开始时，所有19例患者均有多器官功能障碍的证据;中位胆红素为22.3 mg/dL，12例患者有肾功能不全（5例透析依赖性），14例需要补充氧气，8例患者存在脑病。在诊断VOD后中位数6天开始，DF以5 - 60 mg/kg/d的剂量静脉给药，计划的最短疗程为14天。在任何情况下，DF均未因可归因的毒性而停药。未观察到与DF给药相关的严重出血。8例患者（42%）的VOD消退（胆红素<2 mg/dL，其他症状和体征改善）。8例应答者中有6例在+100天后存活，而可比患者中报告的预测存活率为2%。观察到的缓解率、至第+100天的生存率和无显著DF治疗相关毒性是令人信服的，需要进一步评价。
Hepatic veno-occlusive disease (VOD) is the most common of the regimen-related toxicities accompanying stem cell transplantation (SCT). Despite aggressive therapies, including the combination of tissue plasminogen activator (t-PA) and heparin, severe VOD is almost uniformly fatal. Defibrotide (DF) is a polydeoxyribonucleotide with activity in several vascular disorders and, unlike t-PA and heparin, produces no systemic anticoagulant effects. Nineteen patients who developed severe VOD after SCT were treated with DF on a compassionate-use basis. Patients had clinically established VOD and met risk criteria predicting progression and fatality. At the initiation of DF, all 19 patients had evidence of multiorgan dysfunction; median bilirubin was 22.3 mg/dL, 12 patients had renal insufficiency (5 dialysis dependent), 14 required oxygen supplementation, and encephalopathy was present in 8 patients. Beginning a median of 6 days after diagnosis of VOD, DF was administered intravenously in doses ranging from 5 to 60 mg/kg/d for a planned minimum course of 14 days. In no case was DF discontinued for attributable toxicity. No severe hemorrhage related to DF administration was observed. Resolution of VOD (bilirubin <2 mg/dL with improvement in other symptoms and signs) was seen in 8 patients (42%). Six of 8 responders survived past day +100, contrasted with the 2% predicted survival reported in comparable patients. The observed response rate, survival to day +100, and absence of significant DF treatment-associated toxicity are compelling and warrant further evaluation.