The benefits of prophylactic defibrotide: Are the tides turning?

Background: Veno-occlusive disease (VOD) is a life-threatening endotheliopathy that can occur after stem cell transplant (SCT). Numerous risk factors contribute to the development of VOD during SCT, and the role of prophylactic defibrotide (DF) in mitigating these risks remains unclear.

Objective: We compare not only the incidence of VOD development, but also the severity of VOD and survival outcomes between patients who did and did not develop VOD and did or did not receive prophylactic DF.

Study Design: In this single-center retrospective study of 58 pediatric SCT patients from 2008 to 2022, we compare the demographics, risk profiles, and outcomes within three cohorts: Group 1: prophylactic DF and no VOD (n = 5), Group 2: prophylactic DF and development of VOD (n = 6), and Group 3: treatment DF for patients who developed VOD (n = 47).

Results: Patients with VOD who did not receive prophylactic DF had higher severity classification of disease at onset (very severe 80.9% vs. 66.7%, p = .592) and at maximum severity (very severe 89.4% vs. 83.3%, p = .532), as opposed to mild, moderate, or severe categorization compared to those who did not receive prophylactic DF. Patients who developed VOD and did not receive prophylactic DF had a lower 1-year survival probability compared to those who received prophylactic DF and still developed VOD (51.1% vs. 75% alive at 1 year, excluding the two subjects without adequate follow-up time, p = .266).

Conclusion: Although, not statistically significant in our small retrospective study, there is potential overall survival and decreased VOD severity benefits of prophylactic DF.