Defibrotide in the treatment of children with veno-occlusive disease (VOD): a retrospective multicentre study demonstrates therapeutic efficacy upon early intervention

Abstract

Summary:Veno-occlusive disease (VOD) of the liver is a complication observed particularly in patients undergoing hematopoietic stem cell transplantation (HSCT). Defibrotide (DF) is a polydeoxyribonucleotide with aptameric activity on endothelium. We evaluated in a retrospective analysis the efficacy of DF in pediatric patients developing hepatic VOD after HSCT. A total of 45 patients between 0.2 and 20 years (median age: 8.2 years) with hepatic VOD were treated with DF: 22 patients (49%) met risk criteria for severe or progressive disease and 23 (51%) for moderately severe and mild disease. The median duration of DF treatment was 17 days. In all, 34 patients (76%) achieved complete response (CR) with a survival rate of 64% at day 100. CR rate in patients with severe disease was 50% with longterm survival of 36%. The average DF dose in the CR group was 45 mg/kg/day and in the no responder (NR) group 27 mg/kg/day. The use of additional drugs besides DF to treat VOD made no difference in the outcome compared to DF alone. The average interval from diagnosis to start of DF was 1 day in the CR and 5.5 days in NR group. In multivariate analysis, early intervention remained the only significant factor for a CR.

Risk factors for hepatic veno-occlusive disease: a retrospective unicentric study in 116 children autografted after a high-dose BU-thiotepa regimen

“…[24][25][26][27][28] In this population, neither heparin, nor ursodexosycholic acid administration appeared to minimize the risk of HVOD compared to that reported in other series. However, in the present series these drugs were not prospectively evaluated by randomization.…”

Prophylactic defibrotide in allogeneic stem cell transplantation: minimal morbidity and zero mortality from veno-occlusive disease

“…This finding is in keeping with previous reports suggesting that defibrotide can be administered with relative safety in this patient population. [8][9][10][11][12][13]17,18 Hyperbilirubinaemia was noted to be common in post allogeneic SCT in our series. Twenty-nine patients (50%) had a bilirubin X34 mmol/l although they failed to meet the Baltimore criteria.…”

“…Early phase trials of defibrotide in the treatment of moderate to severe VOD have shown promising results with minimal attributable toxicity, encouraging complete response rates (36-50%) and consistent improvements in day þ 100 survival (at 30-60% versus 410% expected). [8][9][10][11][12][13] Several studies have investigated various types of VOD prophylaxis. The role of prophylactic anticoagulation remains uncertain despite a recent meta-analysis.…”

Incidence and management of hepatic severe veno-occlusive disease in 273 patients in a single centre with defibrotide

“…6 Defibrotide, a single-stranded polydeoxyribonucleotide has anti-thrombotic, anti-inflammatory and anti-ischaemic properties and is recommended as the definitive treatment for VOD. [7][8][9][10] We report a single-centre experience based on case note review from over a 45-months period (January 2011 till September 2014) ( Table 1). A total of 273 allogeneic transplants were performed and VOD was diagnosed in 13.…”

“…There is evidence that early treatment with defibrotide improves overall survival. 10 The criteria for diagnosing VOD have been defined more than two decades ago when myeloablative regimens were used for HSCT. Since then many new changes have occurred in the practice of transplantation with respect to conditioning intensity, alternative donors, other organs affected by VOD together with thrombocytopenia with rapid platelet consumption and rapid progression of VOD.…”