title: Defibrotide: a review of its use in severe hepatic veno-occlusive disease following haematopoietic stem cell transplantation.
abstract: Defibrotide (Defitelio(®)) was recently approved in the EU for the treatment of severe hepatic veno-occlusive disease (VOD), also known as sinusoidal obstructive syndrome, in haematopoietic stem cell transplantation (HSCT) therapy. It is indicated in adults, adolescents, children and infants over 1 month of age. Defibrotide is also available in the US via an expanded-access protocol. Defibrotide is thought to protect endothelial cells and restore the thrombo-fibrinolytic balance in VOD. In a multicentre, phase III trial, the complete response rate by day +100 (primary endpoint) was significantly higher, and mortality at day +100 was significantly lower, in patients with severe hepatic VOD and multiorgan failure following HSCT who received intravenous defibrotide 6.25 mg/kg every 6 h than in a group of historical controls. The efficacy of defibrotide in severe hepatic VOD following HSCT was also supported by findings from a phase II dose-finding study, compassionate-use data and information provided from an independent transplant registry. Intravenous defibrotide was generally well tolerated in patients with severe hepatic VOD following HSCT, and was not associated with an increased risk of haemorrhagic adverse events. In conclusion, defibrotide is the only agent approved (in the EU) for use in severe hepatic VOD following HSCT and represents a useful advance in the treatment of this condition.
authors.affiliation: Springer, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand, demail@springer.com.
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Keating
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006504:Hepatic Veno-Occlusive Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D006801:Humans; D011089:Polydeoxyribonucleotides / Q000627:therapeutic use*; D012720:Severity of Illness Index
chemical_list: D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; C036901:defibrotide