Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: update on defibrotide and other current investigational therapies.
Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), remains one of the most serious and common complications after myeloablative hematopoietic stem cell transplantation (HSCT). Clinical diagnosis of hepatic VOD is based on the clinical triad of (1) painful hepatomegaly, (2) hyperbilirubinemia and (3) unexplained fluid retention. While milder cases usually resolve spontaneously, severe VOD is associated with a grim prognosis. Defibrotide (DF), a polydisperse mixture of single-stranded oligonucleotide with antithrombotic and fibrinolytic effects on microvascular endothelium, has emerged as an effective and safe therapy for patients with severe VOD. Multiple studies, including a recent large international multicenter phase II clinical trial, have demonstrated 30-60% complete remission rates with DF, even among patients with severe VOD and multiorgan failure. This article will review our current understanding of hepatic VOD, and update the clinical trial experience with DF and other potential therapies for this feared transplant complication.
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Department of Adult Oncology, Center for Hematologic Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. vincent_ho@dfci.harvard.edu
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D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006504:Hepatic Veno-Occlusive Disease / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology; D011089:Polydeoxyribonucleotides / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D011089:Polydeoxyribonucleotides; C051321:SERPINE1 protein, human; C036901:defibrotide