title: Update on the use of  defibrotide.
abstract: BACKGROUND
  Defibrotide is a polydisperse oligonucleotide obtained from porcine intestinal mucosa and prepared by controlled depolymerization of DNA. It is a nucleic acid polymer, predominantly single-stranded, which has anti-ischemic and anti-thrombotic properties.
  
  
  METHODS
  The efficacy and safety of defibrotide in the treatment of veno-occlusive disease (VOD) occurring after high-dose chemotherapy and hematopoietic stem-cell transplantation is now well established in Phase II - III trials. A recent randomized, Phase III trial in pediatric patients has also demonstrated its role in the prevention of VOD. Preclinical studies reported the inhibitory effects of defibrotide on myeloma cells' growth through an antiangiogenic action and a regulation of the tumor-microenvironment interactions. A recent Phase II trial underlines the efficacy and safety of defibrotide-thalidomide-melphalan combination in the treatment of relapsed/refractory multiple myeloma.
  
  
  CONCLUSIONS
  Defibrotide may be effective in the prophylaxis and the treatment of veno-occlusive disease. Recent experimental results suggest that defibrotide may belong to the new generation of anti-cancer drugs that can prevent tumor angiogenesis. In multiple myeloma, defibrotide may overcome the prothrombotic effect of thalidomide on endothelial cells. Further preclinical and clinical investigations are needed to assess the precise role of defibrotide in the treatment of patients with multiple myeloma.
authors.affiliation: S. Luigi Gonzaga Hospital, Unit of Hematology, Orbassano, Torino, Italy.
authors.forename: Tommasina
authors.initials: T
authors.lastname: Guglielmelli
authors.forename: Sara
authors.initials: S
authors.lastname: Bringhen
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D011089:Polydeoxyribonucleotides / Q000627:therapeutic use*
chemical_list: D052157:Aptamers, Nucleotide; D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; C036901:defibrotide