Clinical outcomes of early defibrotide discontinuation: a single-center case series

Introduction Veno-occlusive disease (VOD) is a life-threatening complication of hematopoietic stem cell transplant (HCT). Defibrotide is FDA approved for the treatment of patients with VOD with renal or hepatic dysfunction after HCT. The product labeling dictates a minimum of 21 days of treatment. However, use of recently updated diagnostic criteria has allowed for earlier treatment initiation which may result in more rapid clinical improvement. Continuing defibrotide beyond achievement of a complete response has the potential for treatment-related adverse events as well as increased cost. Our center has recently adjusted practice to discontinue defibrotide upon VOD resolution, regardless of meeting the 21-day treatment minimum. Methods We hereby summarize our single-center experience using defibrotide 6.25 mg/kg IV every 6 hours for treatment of VOD for <21 days of therapy due to resolution of VOD. All patients were transplanted between 2019-2023. Patients were diagnosed with VOD using either the Baltimore (pre-2021) or Cairo-Cooke (post-2021) criteria and all patients received ursodiol as VOD prophylaxis from conditioning until day +30. Results Four patients were eligible for inclusion with median age of 38.5 years (range: 23-54). All patients received a busulfan-containing myeloablative conditioning regimen and peripheral blood HCT. Two patients received HCT from matched unrelated donors and remaining 2 were a matched related and a haploidentical donor HCT. The majority of patients (75%) had reversal of portal venous flow on abdominal ultrasound and notably, 2 of the 3 patients had anicteric VOD at time of initial diagnosis. Three patients developed renal dysfunction as a result of VOD. Median start date of defibrotide was day +14.5 days post-HCT (range: 12-22). Defibrotide was discontinued in all patients when VOD signs/symptoms had resolved with a median duration of treatment of 12 days (range: 9-13). No patients experienced recurrence of VOD and all patients remain alive at last follow-up. A summary of patients’ pertinent laboratory data during VOD course are summarized in Figure 1. Conclusion Patients with severe VOD following HCT have increased risk of transplant-related mortality and there is unclear guidance on the most appropriate time to initiate defibrotide treatment. Our findings confirm that patients do well with initiation of defibrotide based on updated diagnostic criteria and are able to discontinue treatment earlier than 21 days without recurrence. Decreasing duration of defibrotide treatment could both improve patient outcomes and reduce overall health care costs. Our findings are limited by being a small, single-center retrospective review. However, the findings do warrant consideration for using resolution of VOD as the criteria for defibrotide discontinuation in real-world practice.