Recent developments with defibrotide for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome

Abstract

Introduction: Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening condition associated with endothelial cell damage due to hematopoietic cell transplantation (HCT) conditioning or chemotherapy not associated with HCT. Defibrotide is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post-HCT in the United States and Canada, and severe hepatic VOD/SOS in patients aged >1 month in the European Union. Areas covered: VOD/SOS results from prolonged endothelial cell activation from exposure to chemotherapy or radiotherapy. PubMed was searched for articles on defibrotide without publication date restrictions. In vitro evidence suggests defibrotide has a protective effect on endothelial cells. The efficacy of defibrotide for the treatment of VOD/SOS with multi-organ dysfunction has been shown in clinical trials. Defibrotide has a favorable safety profile comparable to best supportive care in patients with severe forms of VOD/SOS. Expert opinion: As defibrotide treatment for VOD/SOS is most effective when initiated early, medical teams should familiarize themselves with the risk factors for VOD/SOS development and be able to recognize early signs and symptoms. Preclinical data indicate that defibrotide has a protective effect on endothelial cells that may contribute to its efficacy in VOD/SOS and that may render the drug applicable for other indications.

Early and late-onset veno-occlusive disease/sinusoidal syndrome post allogeneic stem cell transplantation – a real-world UK experience

“…Our data are also in‐line with the findings of the T‐IND study suggesting that the outcomes of late‐onset VOD, despite being classed as “very severe” in our cohort, appear comparable to those of classical VOD when managed with Defibrotide; although delayed initiation of treatment that is >3 days in the late‐onset VOD cohort may be associated with relatively higher mortality. Impact of earlier Defibrotide intervention is further evidenced with published T‐IND post hoc analysis and systematic reviews which shows significantly poor survival of patients with delayed Defibrotide initiation compared to those who received it early 5,19,20 …”

Biliary Rhabdomyosarcoma in Pediatric Patients: A Systematic Review and Meta-Analysis of Individual Patient Data

“…Late adverse effects of RT in children have been shown by many studies (51)(52)(53). This has special implications in pediatric patients with BRMS, as unavoidable hepatotoxicity of chemotherapy is aggravated by liver radiation (33,39,40,54,55). EBRT involving the liver has been identified as independent risk factor for acute and late hepatic complications (39,40,55).…”

“…This has special implications in pediatric patients with BRMS, as unavoidable hepatotoxicity of chemotherapy is aggravated by liver radiation (33,39,40,54,55). EBRT involving the liver has been identified as independent risk factor for acute and late hepatic complications (39,40,55). Thus, one aim of future studies should be to investigate minimally needed radiation doses and to stratify patient subgroups for those who do need and those who do not need EBRT for local tumor control.…”