Real-World Outcome of Defibrotide Treatment for Severe Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication following hematopoietic cell transplantation (HCT), with a markedly poor prognosis in patients with severe or very severe presentations. Defibrotide (DF) is the sole approved treatment for severe to very severe VOD/SOS, but real-world evidence remains limited, particularly in East Asian populations. We retrospectively analyzed 73 adult patients with severe or very severe VOD/SOS treated with DF between 2016 and 2023 at a single tertiary center in Korea. Diagnosis and grading were based on the revised European Society for Blood and Marrow Transplantation criteria. During the study period, national reimbursement guidelines for DF evolved from requiring ≥4 of 6 severity criteria to ≥2 of 5 severity criteria, allowing earlier initiation of treatment. The median time from HCT to diagnosis of VOD/SOS was 24 days (range, 1 to 843 days), and DF was administered within a median of 1 day after diagnosis. At DF initiation, 40 patients were classified as severe and 33 were classified as very severe; disease progression resulted in 53 patients reaching the very severe category. The overall response rate was 46.5%, and complete resolution was achieved in 39.7% of cases. The 100-day overall survival was 34.2%, significantly higher in the patients receiving DF within 2 days of diagnosis (36.0% versus 17.4%; P = .049). High total bilirubin levels at diagnosis and at the worst disease period were strongly associated with poor long-term survival regardless of severity criteria. These data provide real-world support for the early use of DF and suggest the prognostic utility of total bilirubin level in guiding treatment for VOD/SOS following HCT.