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Haematology Veno-occlusive Disease Defibrotide – A New Treatment Approach for Severe Veno-occlusive Disease Katrina Mountfort 1 Expertly Reviewed by the Symposium Speakers: Mohamad Mohty 2,3 and Elisabeth Wallhult 4 1. Senior Medical Writer, Touch Medical Media, Reading, UK; 2. Professor of Hematology, Saint-Antoine Hospital, Paris, France; 3. Head of the Hematology and Cellular Therapy Department, University Pierre and Marie Curie, Paris, France; 4. RN and Quality Manager, Section of Haematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden Abstract Severe veno-occlusive disease (VOD) is a serious and life-threatening complication of haematopoietic stem cell transplantation (HSCT), for which the standard of care has until recently been supportive care. VOD is the result of a primary injury to sinusoidal endothelial cells and severe VOD is characterised by sinusoidal narrowing and occlusion, which leads to portal hypertension, multi-organ failure (MOF) and, ultimately, death. Defibrotide regulates multiple pathways involved in the pathological processes underlying VOD and is the first drug to be approved in Europe for the treatment of severe VOD. Defibrotide is indicated for the treatment of severe hepatic VOD in HSCT therapy in adults and infants aged over 1 month. A phase III study found significant increases in complete response (CR) and survival with defibrotide compared with historical controls. These data together with earlier studies and an ongoing expanded access protocol in a large patient cohort demonstrate improved outcomes with defibrotide in severe VOD and highlight the importance of treatment with defibrotide. Keywords Veno-occlusive disease, defibrotide, haematopoietic stem cell transplantation Disclosure: Katrina Mountfort is an employee of Touch Medical Media. Mohamad Mohty received research support and lectures honoraria from Gentium/JAZZ Pharmaceuticals whose product is discussed in this manuscript. Elisabeth Wallhult has received honorarium from Gentium/Jazz Pharmaceuticals for participation in this symposia and has no other disclosures or conflicts of interest to declare. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Received: 5 December 2014 Accepted: 4 March 2015 Citation: European Oncology & Haematology, 2015;11(1):11–4 Correspondence: Katrina Mountfort, Touch Medical Media, The White House, Mill Road, Goring-on-Thames, RG8 9DD, UK. E: Support: This report is based on two satellite symposia and a press event supported by Gentium at the 40th Annual Meeting of the European Society for Blood and Marrow Transplantation meeting in Milan, Italy on 30 March to 2 April 2014. The publication of this report and medical writing assistance was supported by Jazz Pharmaceuticals. Haematopoietic stem cell transplantation (HSCT) has become the standard of care for many haematological malignancies, selected solid tumours and some non-malignant disorders. 1 However, it can be associated with serious complications, in particular, veno-occlusive disease (VOD). Approximately 14  % of HSCT patients develop VOD, although incidences of up to 60 % have been reported. 2,3 Incidence is higher in children and is partly due to certain malignant and inherited diseases that are associated with a substantially increased risk of VOD during HSCT. 4 VOD can also occur in cancer patients undergoing aggressive chemotherapy regimens and has been reported after solid organ transplantation. VOD places a significant burden on healthcare providers and can add considerable additional expense to HSCT costs. 5 VOD presents with different spectrums of severity, from mild VOD, which is self-limiting and requires no treatment, to severe VOD, which is associated with a mortality of over 80 %. 2,6 In October 2013, the European Commission granted marketing authorisation for defibrotide (Defitelio ® Gentium SpA) for the treatment of severe hepatic VOD in HSCT therapy in adults and infants aged over 1 month. Defibrotide is Tou ch ME dical ME d ia the first drug to be approved for severe VOD in Europe. In context with the launch of Defibrotide in Europe, two satellite symposia and a press event were held at the 40th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) on the 31st March and 1st April 2014 in Milan, Italy. This article, based on presentations at the EBMT meeting, will describe the pathophysiology, signs and symptoms of VOD and the use of defibrotide in the treatment of severe VOD. Clinical Manifestations of Veno-occlusive Disease Severe VOD is defined as VOD with the presence of multi-organ failure (MOF). 2 This can include pulmonary failure (oxygen saturation [S0 2 ] <90  % and/or ventilator dependence); renal failure (doubling of serum creatinine and/or dialysis dependence) and central nervous system (CNS) abnormalities (confusion, encephalopathy and coma). Symptoms of VOD can include painful hepatomegaly, jaundice (serum bilirubin ≥2  mg/dl, 34.2 mmol/l), fluid retention, weight gain (≥5 %), ascites, usually with onset in the first 3–4 weeks following HSCT, and the absence of other causes. 4,7 Certain clinical signs of VOD, including a rapid increase of bilirubin level 11