Low, fixed dose defibrotide in management of hepatic veno-occlusive disease post stem cell transplantation.

Publication date: Available online 25 April 2017
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Bhausaheb Bagal, Arun Chandrasekharan, Aliya Chougle, Navin Khattry
Objective/backgroundHepatic veno-occlusive disease (VOD) is well recognized potentially serious regimen-related toxicity seen after stem cell transplantation. Severe VOD is associated with poor long term outcomes with very high mortality. Besides supportive care, only defibrotide has been found to be effective in the management of VOD. The recommended dose of defibrotide is 25 mg/kg/d but there has been no classical dose finding study done for this drug. A higher dose of defibrotide is associated with increased risk of bleeding and this drug is prohibitively expensive. We report our experience of using fixed low dose of defibrotide in patients with VOD.MethodsWe retrospectively evaluated 511 patients who underwent stem cell transplant at our center from November 2007 and December 2015. All patients received ursodeoxycolic acid as VOD prophylaxis. Modified Seattle criterion was used for diagnosis and severity grading of VOD. Patients developing VOD were initially treated with furosemide and adequate analgesia. Defibrotide was started within 12 to 24 hours of diagnosis of VOD. All adult patients received defibrotide at a fixed dose of 200 mg twice daily while two children were given dose of 100 mg and 50 mg twice daily.ResultsNine (1.7%) of our patients developed VOD. Daily dose of defibrotide ranged from 5 mg /kg/d to 20 mg/kg/d till resolution of VOD. All patients had complete resolution of VOD. None of our patients required ventilator support or dialysis. No episodes of bleeding were observed. No dose response relationship was observed between defibrotide dose and time to resolution of VOD.ConclusionLow fixed dose defibrotide initiated early seems to be effective and safe in treatment of VOD. This is relevant in a resource limited setting and warrants prospective evaluation.



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