Ho Vincent T, Linden Erica, Revta Carolyn, Richardson Paul G
Department of Adult Oncology, Center for Hematologic Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Semin Thromb Hemost. 2007 Jun;33(4):373-88. doi: 10.1055/s-2007-976173.
Veno-occlusive disease (VOD) of the liver remains one of the most feared complications associated with high-dose chemotherapy and hematopoietic stem cell transplantation (SCT). As a clinical syndrome characterized by fluid retention, hyperbilirubinemia, and painful hepatomegaly, VOD incidence varies widely, but it is universally recognized that severe cases of VOD have an extremely poor prognosis, with mortality at day 100 after SCT in excess of 80%. Systemic anticoagulant and thrombolytic therapies have been tested extensively in this disease, but are largely ineffective and are associated with significant bleeding complications. In recent years, defibrotide (DF; a polydisperse oligonucleotide derived from porcine intestinal mucosa with antithrombotic and protective properties on the microvasculature but minimal hemorrhagic risk) has emerged as a promising therapy for VOD. In large, multicenter, international phase I/II trials targeting patients with severe VOD, DF has been associated with complete response rates between 36 and 60%, survival past transplant day 100 in the range of 32 to 50%, and few significant attributable side effects. On the basis of these encouraging results, a pivotal, prospective, multinational, phase III trial of DF is underway in patients with severe VOD, and should provide validation of this agent as a therapy for established disease with a high risk of mortality. This article reviews our current understanding of hepatic VOD after SCT and provides a summary of the data to date on the use of DF as both therapy and prophylaxis for this disease.
肝静脉闭塞病（VOD）仍然是与大剂量化疗和造血干细胞移植（SCT）相关的最可怕并发症之一。作为一种以液体潴留、高胆红素血症和肝肿大疼痛为特征的临床综合征，VOD的发病率差异很大，但普遍认为严重的VOD预后极差，SCT后100天的死亡率超过80%。全身抗凝和溶栓疗法已在这种疾病中进行了广泛测试，但大多无效，且伴有严重的出血并发症。近年来，去纤苷（DF；一种从猪肠黏膜中提取的多分散寡核苷酸，对微血管具有抗血栓和保护作用，但出血风险极小）已成为一种有前景的VOD治疗方法。在针对严重VOD患者的大型、多中心、国际I/II期试验中，DF的完全缓解率在36%至60%之间，移植后100天的生存率在32%至50%之间，且几乎没有明显的可归因副作用。基于这些令人鼓舞的结果，一项针对严重VOD患者的关键、前瞻性、多国III期试验正在进行，该试验应能验证这种药物作为一种治疗具有高死亡风险的已确诊疾病的疗法的有效性。本文回顾了我们目前对SCT后肝VOD的认识，并总结了迄今为止关于DF作为这种疾病的治疗和预防药物的数据。
