Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation

Paul G. Richardson, Angela R. Smith, Brandon M. Triplett, Nancy A. Kernan, Stephan A. Grupp, Joseph H. Antin, Leslie Lehmann, Maja Miloslavsky, Robin Hume, Alison L. Hannah, Bijan Nejadnik, Robert J. Soiffer

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)112-118
Number of pages7
JournalBritish journal of haematology
Volume178
Issue number1
DOIs
StatePublished - Jul 2017

Keywords

  • defibrotide
  • sinusoidal obstruction syndrome
  • survival
  • treatment initiation
  • veno-occlusive disease

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