Effects of Prophylactic Defibrotide for Veno-Occlusive Disease in Hematopoietic Stem Cell Transplantation

Defibrotide has recently been successfully used to treat veno-occlusive disease (VOD). We report the use of intravenous defibrotide for VOD prophylaxis in 49 patients who received hematopoietic stem cell transplantation (HSCT). This group was compared with a control group of 49 patients who underwent HSCT without defibrotide prophylaxis.

Data were collected retrospectively on 98 patients undergoing HSCT at the National Cancer Center, Goyang, Korea, between August 2005 and July 2008. During this period, defibrotide was randomly supplied to 49 patients free of charge by the compassionate use program. For 49 patients, VOD prophylaxis with 200 to 400 mg of defibrotide (25 mg/kg/day in children weighing less than 30 kg) administered intravenously 3 or 4 times daily was initiated from the start of conditioning and continued until 28 days post-HSCT.

VOD was diagnosed in 5 of 98 total patients (5.1%) at a median of 11 days post-HSCT (range: 10–14 days). VOD was graded as mild in 2 patients, moderate in 1, and severe in 2. The incidences of engraftment syndrome, thrombotic microangiopathy and VOD were not significantly different between the defibrotide group and the control group, although absolute incidences of each syndrome were lower in the defibrotide group. Patients who received prophylactic defibrotide showed earlier platelet engraftment (p<0.01) and lower activated prothrombin time (p=0.02) after HSCT. There was no day 100 treatment-related mortality (TRM) in the defibrotide group. Day 100 TRM occurred in two patients who did not receive defibrotide for VOD prophylaxis during allogeneic HSCT. Each patient was diagnosed with mild or severe VOD, and the direct causes of death were infection or VOD. Of the patients who were diagnosed with VOD, the overall survival at 100 days post HSCT was significantly higher in the defibrotide group compared to the control group (100% vs. 33.3 ± 27.2%, p<0.01). Defibrotide was well tolerated and was not discontinued in any patients. There was no grade 3 or 4 toxicity related to defibrotide or any worsening of clinical bleeding.

Our data showed that the use of prophylactic defibrotide is safe and may have beneficial effects of defibrotide on hepatic endothelial damage following HSCT, with no TRM in defibrotide group. Considering there is no consensus on when to start treatment if a patient shows clinical features suggesting VOD, it could be important to use prophylactic defibrotide in advance for improved VOD outcomes.

No relevant conflicts of interest to declare.