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Vol. 42. Issue S2.
Pages 291-292 (November 2020)
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Vol. 42. Issue S2.
Pages 291-292 (November 2020)
483
Open Access
DEFIBROTIDE TREATMENT IN PAEDIATRIC PATIENTS WITH SEVERE/VERY SEVERE VENO-OCCLUSIVE DISEASE/SINUSOIDAL OBSTRUCTION SYNDROME AFTER HAEMATOPOIETIC CELL TRANSPLANTATION: DEFIFRANCE INTERIM RESULTS
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V. Gandemera, P. Schneiderb, A. Sirventc, R. Martind, V. Bouvatiere, M. Labopinf, M. Mohtyf
a University Hospital of Rennes, Rennes, France
b University Hospital, Rouen, France
c Hôpital Arnaud de Villeneuve, Montpellier, France
d Jazz Pharmaceuticals, Oxford, United Kingdom
e Jazz Pharmaceuticals, Lyon, France
f Hôpital St Antoine, Sorbonne University, INSERM UMRs 938, Paris, France
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Objectives: Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially fatal complication of haematopoietic cell transplantation (HCT) conditioning that may also develop after high-dose chemotherapy. Defibrotide is approved in Brasil and the US for adult and paediatric patients (aged >1 month in Brasil) with hepatic VOD/SOS with renal or pulmonary dysfunction post-HCT, and in the EU for patients aged >1 month with severe hepatic VOD/SOS post-HCT. The DEFIFrance study is collecting real-world data on outcomes in patients treated with defibrotide across France. This interim analysis evaluated a subgroup of paediatric patients (<18 years) with severe/very severe VOD/SOS post-HCT who were treated with defibrotide. Material and methods: DEFIFrance is a multicentre, post-marketing study collecting retrospective and prospective real-world data on patients receiving defibrotide at 53 HCT centres in France since July 2014; this analysis includes data collected from 36 active HCT centres. Criteria used for VOD/SOS diagnosis were at the discretion of the treating physician based on their clinical expertise; severity was adjudicated by an expert steering committee member according to EBMT criteria. Primary endpoints included Kaplan-Meier (KM)–estimated Day 100 survival rate post-HCT and Day 100 complete response (CR; total serum bilirubin <2 mg/dL and resolution of multi-organ failure [MOF] per investigators’assessment) in patients with severe/very severe VOD/SOS post-HCT. Secondary endpoints included evaluation of adverse events (AEs) of interest, irrespective of their relationship to treatment. Results: As of 8 November 2018, 324 patients were included in DEFIFrance. Of these, 41 paediatric patients had VOD/SOS post-HCT, of which 23 had severe/very severe VOD/SOS and were included in this analysis. Median age was 8.5 (range, 0.4–17.5) years. MOF occurred in 5 (22%) patients. The KM–estimated Day 100 post-HCT survival rate was 85% (severe [n = 14]: 100%; very severe [n = 9]: 53%); estimated survival rates were 68% and 55% at 6 and 12 months, respectively. The Day 100 post-HCT CR rate was 81% in patients with severe/very severe VOD/SOS. Among evaluable patients with severe (n = 14) and very severe (n = 7) VOD/SOS, Day 100 CR rates were 93% and 57%, respectively. Day 100 VOD/SOS-related mortality was 15%; deaths after Day 100 resulted from causes other than VOD/SOS. AEs of interest occurred in 15/23 patients; common events included infection (n = 7/23) and respiratory symptoms (n = 6/23). Discussion: The DEFIFrance study represents the largest collection of real-world data on the use of defibrotide. This subgroup analysis focused on paediatric patients who received defibrotide for the treatment of severe or very severe VOD/SOS (per EBMT criteria) post-HCT. Limitations of DEFIFrance include some retrospective data collection and limited data at the time of this interim analysis. Conclusion: Prognosis is poor for patients with untreated, very severe VOD/SOS post-HCT. Among paediatric patients treated with defibrotide post-HCT for VOD/SOS, outcomes were better in severe versus very severe disease, highlighting the importance of early VOD/SOS diagnosis and treatment initiation. The incidence of AEs of interest was consistent with previous studies.

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Hematology, Transfusion and Cell Therapy
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