Cost-Effectiveness of Defibrotide in the Prophylaxis of Veno-Occlusive Disease after Pediatric Allogeneic Stem Cell Transplantation

Abstract

Veno-occlusive disease (VOD) remains a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Prophylactic use of defibrotide (DF) might further reduce VOD rates but has no impact on the incidence of severe VOD or VOD-associated mortality. We investigated the cost-effectiveness of prophylactic DF according to the British Committee for Standards in Haematology/British Society for Blood and Marrow Transplantation guidelines in 348 children who underwent transplantation between 2001 and 2014 in our hospital, 138 of whom were at risk for VOD. The VOD incidence was 7.4% for the total cohort. Patients at risk had a higher incidence of VOD compared with patients without risk factors (15.2% versus 2.4%, P < .0001). VOD occurred more often in patients after busulfan-based myeloablative conditioning than in patients after total body irradiation (11.2% versus 3.5%, P = .001). Donor types or the transplantation-related mortality (TRM) risk score did not correlate with VOD incidence. In 81% of patients who responded to therapeutic DF, VOD resolved completely. Overall VOD-associated mortality was .3% for the complete cohort, 3.7% for patients diagnosed with VOD, and 20% for patients with severe VOD. Neither the cumulative incidence of TRM (19% ± 8% versus 17% ± 2%, P = .706) nor the median length of hospitalization differed between patients with VOD and patients without. The median costs per HSCT in patients with VOD were about one-third higher than the overall median costs per transplantation at our institution. The calculated total costs of prophylactic DF treatment for 138 patients at risk was almost 6 times as high as the incremental costs for patients with VOD. We conclude that prophylactic DF for children at risk for VOD is not cost-effective with respect to TRM and length of hospital stay.

Defibrotide treatment but not prophylaxis is useful in hepatic sinusoidal obstruction syndrome in children undergoing autologous stem cell transplant following high‐dose chemotherapy: A single‐center experience from the Royal Marsden Hospital, UK

“…Though previous studies 6,9 using DF prophylaxis for longer periods than us have shown protective effect, most of them have included allogeneic 6 or both allogeneic and autologous transplant patients 9 . It is unclear if extending the duration of DF prophylaxis (beyond day +14) would have been helpful in our cohort, but it would have surely led to significant escalation of cost 26 …”

“…UDCA is an inexpensive and safe intervention as compared with DF, which is costly and has been associated with potentially hazardous adverse effects such as bleeding. A recent paper on the prophylactic use of DF in children undergoing allogenic stem cell transplant has not shown DF to be a cost‐effective intervention either 26 …”

Defibrotide: An Oligonucleotide for Sinusoidal Obstruction Syndrome

“…45 Recently, a cost-effectiveness analysis of defibrotide prophylaxis was conducted in 348 children undergoing HCT. 46 The incidence of VOD in the cohort was 7.4%. Risk factors for VOD/SOS were present in 39.6% of patients, and the incidence of VOD/SOS was significantly greater in patients with risk factors when compared with those without (15.2% vs 2.4%, P < 0.0001).…”

“…13 Although there are efficacy data to support this strategy, cost-effectiveness data do not support the use of defibrotide prophylaxis in all patients receiving HCT. 46 Additionally, the optimal dose, timing, and duration for prophylaxis have yet to be established. A phase 3 study of defibrotide compared with best supportive care for VOD/ SOS prevention in adult and pediatric patients is currently recruiting, with a planned primary outcome of VOD-free survival at day +30 and secondary outcome of VOD-free survival at day +100 post-HCT.…”

The Prophylaxis of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome With Defibrotide After Hematopoietic Stem Cell Transplantation in Children: Single Center Experience

“…In addition, several studies have examined DF prophylaxis can reduce the incidence of VOD/SOS in high-risk patients. [12][13][14][15] With this study, we report our experience with the prophylactic use of DF in pediatric HSCT recipients who were considered at high-risk for VOD/ SOS.…”