Use of defibrotide in the treatment and prevention of veno-occlusive disease.

Hepatic veno-occlusive disease (VOD) is one of the most important complications of high-dose chemotherapy and stem cell transplantation. VOD is a clinical syndrome characterized by jaundice, hepatic enlargement and fluid retention typically seen by day +30 after transplantation. Severe VOD is complicated by multiorgan failure and a high mortality rate approaching 100%. Defibrotide (DF) is a novel agent with both antithrombotic and fibrinolytic properties that has emerged as an effective therapy for severe VOD. In Phase II studies, treatment of severe VOD has resulted in complete responses of 30-60% and survival past day 100 ranging between 32-50%. A Phase III, historically controlled study of DF for treatment of severe VOD has recently been completed and results are awaited with interest. In addition, DF may be effective prophylaxis for VOD in high-risk patients. This review will focus on a summary of the pharmacology of DF and the clinical evidence for its use in VOD.