Summary Background Hepatic veno-occlusive disease is a leading cause of morbidity and mortality after haemopoietic stem-cell transplantation (HSCT). We aimed to assess whether defibrotide can reduce ...the incidence of veno-occlusive disease in this setting. Methods In our phase 3 open-label, randomised controlled trial, we enrolled patients at 28 European university hospitals or academic medical centres. Eligible patients were younger than 18 years, had undergone myeloablative conditioning before allogeneic or autologous HSCT, and had one or more risk factor for veno-occlusive disease based on modified Seattle criteria. We centrally assigned eligible participants on the basis of a computer-generated randomisation sequence (1:1), stratified by centre and presence of osteopetrosis, to receive intravenous defibrotide prophylaxis (treatment group) or not (control group). The primary endpoint was incidence of veno-occlusive disease by 30 days after HSCT, adjudicated by a masked, independent review committee, in eligible patients who consented to randomisation (intention-to-treat population), and was assessed with a competing risk approach. Patients in either group who developed veno-occlusive disease received defibrotide for treatment. We assessed adverse events to 180 days after HSCT in all patients who received allocated prophylaxis. This trial is registered with ClinicalTrials.gov , number NCT00272948. Findings Between Jan 25, 2006, and Jan 29, 2009, we enrolled 356 eligible patients to the intention-to-treat population. 22 (12%) of 180 patients randomly allocated to the defibrotide group had veno-occlusive disease by 30 days after HSCT compared with 35 (20%) of 176 controls (risk difference −7·7%, 95% CI −15·3 to −0·1; Z test for competing risk analysis p=0·0488; log-rank test p=0·0507). 154 (87%) of 177 patients in the defibrotide group had adverse events by day 180 compared with 155 (88%) of 176 controls. Interpretation Defibrotide prophylaxis seems to reduce incidence of veno-occlusive disease and is well tolerated. Thus, such prophylaxis could present a useful clinical option for this serious complication of HSCT. Funding Gentium SpA, European Group for Blood and Marrow Transplantation.
Defibrotide is approved to treat hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) with renal/pulmonary dysfunction following hematopoietic cell transplantation (HCT) in adult ...and pediatric patients in the United States, and to treat severe hepatic VOD/SOS post-HCT in adult and pediatric patients aged >1 month in the European Union. The defibrotide prescribing information warns that defibrotide may increase bleeding risk in VOD/SOS patients. To broaden our understanding of the incidence of bleeding with defibrotide, we performed a meta-analysis of the published literature of defibrotide use outside of the post-HCT VOD/SOS setting. Of 1857 records identified, 125 reported on defibrotide; 23 contained data on bleeding events. The estimated overall incidence of bleeding events was 1% (95% confidence interval CI: 0%-2%) and 8% (95% CI: 3%-14%) in studies using intravenous defibrotide and studies with controls, respectively. The risk ratio for bleeding events with intravenous defibrotide versus controls was 0.36 (95% CI: 0.24-0.52; P < .00001) among studies with data on intravenous defibrotide and controls. This meta-analysis of defibrotide use outside of the post-HCT VOD/SOS setting suggests that the incidence of bleeding with defibrotide is lower than controls.
Highlights 3 to 5 bullet points with a maximum of 85 characters each including spaces • Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) can be severe • Severe VOD/SOS can develop ...unpredictably and can be fatal. • Defibrotide has demonstrated efficacy and safety in treatment of VOD/SOS. • Safety and efficacy were consistent with prior studies of defibrotide in VOD/SOS. • Subgroup results lend support to the 25 mg/kg/day recommended dose for defibrotide.
Abstract Objective We report our experience with use of LVAD as destination therapy for the management of patients with cardiac end-stage Distrophinopaties Methods From February 2011 to February ...2016, 7 patients with Distrophinopaties and dilated cardiomyopathy were assisted with LVAD at our Institution. Median age at surgery was 16.5 years (range 14,2-23,4). A ll patients were pre-operatively evaluated by multidisciplinary team approach. Results All patients survived to hospital discharge. The early post-operative course was characterized by abdominal bleeding (1 patient) and retropharyngeal bleeding (1 patient). Due to abdominal or retropharyngeal bleeding both required post-operative heparin infusion discontinuation for 35 and 33 days respectively. Amongst late complications, one child developed osteolysis and infection at the pedestal site of device which required surgical displacement; one patient required gastrostomy due to poor feeding and another suffered a cerebral stroke treated with percutaneous thrombus aspiration. The last 2 patients did not showed early or late complications. At median FU time of 21.7 months (range 3-45) we have 3 late deaths: one patient died after 45 months for lung infection, the second died for tracheal bleeding after 29 months and the last died for cerebral hemorrhage after 14 months. Conclusions Our experience indicate that the use of VAD as DT in Distrophinopaties patients with end stage DCM is feasible, suggesting that may be a palliative therapy for the treatment of these patients with otherwise no other therapeutic options.
Highlights • Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) can be severe. • Severe VOD/SOS may be associated with multi-organ dysfunction and ≥80% mortality. • Defibrotide has ...demonstrated efficacy in treatment of severe hepatic VOD/SOS. • This has been the largest prospective evaluation of defibrotide for severe VOD/SOS.
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