CP-129 Defibrotide for sinusoidal obstruction syndrome: a single centre experience

Abstract

Background Sinusoidal obstruction syndrome (SOS) is an important non-haematological toxicity in patients who have received chemotherapy for haematopoietic stem cell transplantation (HSCT). In March 2013, European Medicines Agency refused marketing authorisation for the orphan drug defibrotide to prevent and treat SOS. In July 2013, after re-examination, defibrotide had a new positive opinion for marketing authorisation but only for treatment. Purpose To investigate the effectiveness, safety and cost of defibrotide for SOS. Materials and methods Retrospective observational study (Period: January 2009–September 2013). We analysed patients with SOS treated with defibrotide. Response criteria were defined as total serum bilirubin <2 mg/dl and resolution of multiple organ failure (MOF), including renal (recovery of normal creatinine value and lack of dialysis dependence), pulmonary (no oxygen dependence) and central nervous system (absence of encephalopathy) function. Evolution of the Baltimore criteria, including hepatomegaly, ascites and weight gain was measured. Secondary endpoint was survival by 100 days post-HSCT. Adverse events related to defibrotide administration were also retrieved. Results Eleven patients (five adults (mean age: 55.7(SD = 4.3) years) and four children (3.1(SD = 1.3)) received defibrotide at a dose of 6.25 mg/kg every 6 h (two patients received 10 mg/kg/6 h). Median duration of treatment was 9 days (range: 5–25). Overall complete response was achieved in seven patients (63.6%), all four children and only three adults. 45.5% of patients had completely recovered from hepatomegaly at the end of defibrotide administration. Six of the eight patients with ascites and one patient with encephalopathy recovered their normal status. All patients reduced their weight gain after defibrotide treatment. 100 day post-HSCT survival was 72.7%. Three patients presented haemorrhagic episodes during defibrotide treatment (two gastrointestinal episodes and one nasal bleeding). Median cost per patient was 19,180 € (range 5,480–41,100 €). Conclusions According to our limited results, defibrotide is an effective option for SOS treatment in children, although cost per patient is high. Cost-effectiveness studies comparing treatment for SOS with and without defibrotide are needed. No conflict of interest.

Efficacy and Safety of Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

“…Full-text review further excluded eight articles, generating 16 studies in total for the current systematic review and meta-analysis. 17,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] The search process is shown in ►Fig. 1.…”

“…These studies were published from 2000 to 2018. Among the 16 studies, three were abstracts of unpublished studies, 22,29,34 and the other 13 were fully published studies. 17,[23][24][25][26][27][28][30][31][32][33]35,36 The sample size provided a total of 3,002 patients ranging from 11 to 1,000.…”

“…17,[23][24][25][26][27][28][30][31][32][33]35,36 The sample size provided a total of 3,002 patients ranging from 11 to 1,000. Of the included studies, six were conducted in the United States, 17,28,[31][32][33]35 eight in Europe, [22][23][24][25][26]29,30,34 one in Australia, 27 and one in Asia. 36 Eight studies only reported the VOD patients post-HSCT, [22][23][24]26,27,29,34,36 five studies included merely sVOD patients, 17,30,32,35 and three studies provided both VOD and sVOD patients.…”

“…Of the included studies, six were conducted in the United States, 17,28,[31][32][33]35 eight in Europe, [22][23][24][25][26]29,30,34 one in Australia, 27 and one in Asia. 36 Eight studies only reported the VOD patients post-HSCT, [22][23][24]26,27,29,34,36 five studies included merely sVOD patients, 17,30,32,35 and three studies provided both VOD and sVOD patients. 25,28,33 Risk-of-bias assessment of the included studies is presented in ►Supplementary Table S1 (online only).…”

“…25,28,33 Risk-of-bias assessment of the included studies is presented in ►Supplementary Table S1 (online only). When using the modified Newcastle-Ottawa scale to assess the risk of bias of the cohort studies, six studies were considered as low quality, 22,27,29,30,34,35 six were perceived as moderate quality, 17,23,24,26,31,36 and four were regarded as high quality. 25,28,32,33 Primary Outcome: Day þ100 Survival Rate…”