Defibrotide for the prevention and treatment of hepatic veno-occlusive disease after hematopoietic stem cell transplantation; A single center experience

Background: Hepatic veno-occlusive disease (VOD) is a common and serious complication of hemotopoietic stem cell transplantation (HSCT) in children. We aimed to assess prospectively the use of prophylactic defibrotide in pediatric patients undergoing HSCT. Aims: We aimed to assess prospectively the use of prophylactic defibrotide in pediatric patients undergoing HSCT. Methods: In this study, 113 patients who underwent HSCT were given defibrotide prophylaxis as 25mg/kg per day in four divided intravenous infusions over 2h, starting on the same day as the pretransplantation conditioning regimen. The mean duration of use of defibrotide is 25 days as a prophylaxis. Results: In this study, 113 patients were recruited, 66 male patients and 47 female patients, with the average of 9.1 years, range 1-20; 8%infants, 55%children and 37%adolescent. There were 50 patients with thalassemia major, 41 patients with leukemia, 11 patients with aplastic anemia, one patient with Diamond Blackfan anemia, two patients with congenitale dyserythropoetic anemia, one patient with osteopetrosis, four patients with famial hemophagocytic lymphohistiocytosis, two patienrs with severe immune deficiency and one patient with Kostman syndrome. All transplants were allogeneic. No serious side effects were seen. In eight patients developed clinical VOD (Seattle criteria). In these patients, defibrotide dose was increased to a treatment dose of 40-60mg/kg per day. One infant patient with Kostman syndrome died due to hepatic and pulmonary veno-occlusive disease. After 36 months of follow up, 7 patients who developed VOD are being well and no patient have transplant related complications. Summary/Conclusions: Hepatic veno-occlusive disease, which is caused by hepatocyte and sinusoidal vessel endothelium damage, can ocur early after HSCT, and in its severe form, may lead tol iver faillure, hepatorenal syndrom, portal hypertension, and eventually death from multiorgan faillure. In this prospective study, we demonstrated that the use of defibrotide is safe and effective in preventing and treating VOD in pediatric patients at high risk.