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

Defibrotide has been approved in several geographic jurisdictions for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) for years. However, available data on efficacy and safety for its use in VOD are contrasting. We performed a meta-analysis to evaluate the efficacy and safety of defibrotide in the treatment of hepatic VOD/SOS post-hematopoietic stem cell transplantation (HSCT). PubMed and Embase were searched for studies regarding the efficacy and safety of defibrotide in VOD patients. Survival rate at day+100 post-HSCT (D+100 SR), as well as the prognosis, comprising complete response (CR), adverse events including >= 1 adverse event (>= 1 AE), hemorrhage, and serious adverse events (SAEs), were pooled using a random effect model. Sixteen studies involving 3,002 participants were included. Pooled estimates for overall D+100 SR as well as rate of CR, >= 1 AE, hemorrhage, SAEs in VOD patients post-HSCT were 58% (95% CI: 54-62%), 57% (95% CI: 45-68%), 65% (95% CI: 54-75%), 16% (95% CI: 5-27%), 53% (95% CI: 51-55%), respectively, and were 44% (95% CI: 39-48%), 39% (95% CI: 28-50%), 88% (95% CI: 71-100%), 42% (95% CI: 30-55%), 58% (95% CI: 52-64%), respectively, in severe VOD (sVOD) patients. Hemorrhage and hypotension were the most common AEs. Current evidence suggests that defibrotide improves the D+100 SR and CR in VOD/sVOD patients following HSCT. However, the results of this review/meta-analysis were mainly based on data from observational studies, potentially subject to selection bias. Consequently, higher quality randomized control trials and larger prospective cohort studies are warranted.