The Benefits of Prophylactic Defibrotide: Are the Tides Turning?

• Published in: Transplantation and cellular therapy 2024-02, Vol.30 (2), p.S147-S147
• Main Authors: Rahim, Mahvish Qureshi, Rahrig, April L., Dinora, Devin, Harrison, Jessica, Green, Ryanne, Carter, Allie, Skiles, Jodi L.
• Format: Article
• Language: English
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2024.01.047

Veno-Occlusive Disease (VOD) is a life-threatening endotheliopathy that can occur after stem cell transplant (SCT). Current management of VOD includes a combination of supportive care and defibrotide (DF). The use of DF has improved survival of patients with VOD. While there are numerous risk factors that contribute to the development of VOD during SCT, effective interventions to mitigate these risks remain unclear and many patients still die of VOD, despite aggressive management. The use of prophylactic DF for the prevention of VOD remains a clinical controversy within the stem cell transplant community. This study compares the demographics, risk profiles, and outcomes of patients who received DF during their HSCT course either as prophylaxis, treatment, or as both. In this single center retrospective study of pediatric SCT patients from 2008 to 2022, we describe development of VOD within three cohorts: Group 1: Prophylactic DF and no VOD, Group 2: Prophylactic DF and developed VOD, and Group 3: No prophylactic DF and developed VOD. Risk for VOD development was assessed using high risk and very high-risk criteria that was adapted from the HARMONY Trial. The three groups were assessed for the association of prophylactic DF use with VOD incidence, VOD severity, utilization of ICU interventions, cause of death, and overall survival. Fifty-eight patients were included, with 5 in Group 1, 6 in Group 2, and 47 in Group 3. The incidence of VOD in patients undergoing SCT during this time-period was 10% (53/530). All patients in our cohort with Hispanic/Latino ethnicity developed the disease. However, this proportion was not significantly greater than the non-Hispanic ethnicity group (p= 0.575). Patients who met very high-risk criteria were more likely to receive prophylactic DF (p=0.003) and 66.6% developed VOD. Patients who did not receive prophylactic defibrotide were more likely to have a very severe VOD at disease onset (80.9% compared to 66.7%, p=0.592) and at maximum disease severity (89.4% vs. 83.3%, p=0.532). As expected, patients with VOD had lower 1 year survival compared to those without VOD (54.7% vs 80%, p=0.243). Patients who developed VOD and did not receive prophylactic defibrotide had a lower 1-year survival probability compared to those with VOD who received prophylactic defibrotide (51.1% vs 83.3% alive at 1 year, p=0.235). In conclusion, we find that the use of prophylactic DF is not associated with a statistically significant decrease in the