Impact of defibrotide on survival in sinusoidal obstruction syndrome / veno-occlusive disease: a retrospective cohort study comparing two sequential treatment eras

Background Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a serious endothelial injury syndrome following allogeneic hematopoietic stem cell transplantation (allo-HSCT) requiring early diagnosis and treatment. We retrospectively evaluated clinical characteristics, treatments, and outcomes of patients who developed SOS/VOD after allo-HSCT.Methods We included all consecutive patients who developed SOS/VOD after allo-HSCT between January 2010 and October 2023. SOS/VOD was diagnosed according to Seattle, Baltimore, or EBMT criteria, and severity was classified using the EBMT criteria. Patients treated with recombinant thrombomodulin (rTM) between January 2010 and August 2019 were compared with those treated with defibrotide between September 2019 and October 2023.Results Among 755 cases, 48 developed SOS/VOD: 15 treated with rTM and 33 with defibrotide. Median ages were 50 years in rTM group and 55 years in defibrotide group, and median days to onset were 13 and 17, respectively. There was no significant difference in disease stage at transplantation or SOS/VOD severity at diagnosis. At 100 days post-onset, overall survival (OS), non-relapse mortality, and SOS/VOD mortality were 20.0% vs 46.9% (p = 0.17), 66.7% vs 54.5% (p = 0.609), and 46.7% vs 31.2% (p = 0.364) in the rTM and defibrotide groups, respectively. In multivariate analysis adjusted for age and conditioning intensity, defibrotide treatment was associated with improved OS (hazard ratio, 0.41; 95% confidence interval, 0.18–0.92, p = 0.032). Review of most severe cases suggested an association between inflammatory status and the clinical course of SOS/VOD.Conclusion Defibrotide treatment was associated with improved outcome in SOS/VOD. Inflammatory status appeared to be related to disease onset and resolution.