Earlier defibrotide initiation post‐diagnosis of veno‐occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation. (26th April 2017)

• Record Type: Journal Article
• Authors: Richardson, Paul G.; Smith, Angela R.; Triplett, Brandon M.; Kernan, Nancy A.; Grupp, Stephan A.; Antin, Joseph H.; Lehmann, Leslie; Miloslavsky, Maja; Hume, Robin; Hannah, Alison L.; Nejadnik, Bijan; Soiffer, Robert J.
• Is Part Of: British journal of haematology. Volume 178:Number 1(2017)
• Page Start: 112
• Page End: 118
• Publication Date: 2017-04-26
• Subjects: defibrotide -- veno‐occlusive disease -- sinusoidal obstruction syndrome -- treatment initiation -- survival; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.14727
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: Hepatic veno‐occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a progressive, potentially fatal complication of conditioning for haematopoietic stem cell transplant (HSCT). The VOD/SOS pathophysiological cascade involves endothelial‐cell activation and damage, and a prothrombotic‐hypofibrinolytic state. Severe VOD/SOS (typically characterized by multi‐organ dysfunction) may be associated with >80% mortality. Defibrotide is approved for treating severe hepatic VOD/SOS post‐HSCT in the European Union, and for hepatic VOD/SOS with renal or pulmonary dysfunction post‐HSCT in the United States. Previously, defibrotide (25 mg/kg/day in 4 divided doses for a recommended ≥21 days) was available through an expanded‐access treatment protocol for patients with VOD/SOS. Data from this study were examined post‐hoc to determine if the timing of defibrotide initiation post‐VOD/SOS diagnosis affected Day +100 survival post‐HSCT. Among 573 patients, defibrotide was started on the day of VOD/SOS diagnosis in approximately 30%, and within 7 days in >90%. The relationship between Day +100 survival and treatment initiation before/after specific days post‐diagnosis showed superior survival when treatment was initiated closer to VOD/SOS diagnosis with a statistically significant trend over time for better outcomes with earlier treatment initiation ( P < 0·001). These results suggest that initiation of defibrotide should not be delayed after diagnosis of VOD/SOS.