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Published on: September 6, 2017
Evaluation of Prophylactic Defibrotide Use in Pediatric Hematopoietic Stem Cell Transplant Recipients: A Multicenter
Archana Ramgopal1, Tsuyoshi Fujita1, Breana K Goscicki1
1Division of Hematology, Oncology, and Stem Cell Transplantation, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.
Insights
Prophylactic defibrotide did not reduce sinusoidal obstruction syndrome (SOS) incidence in pediatric hematopoietic stem cell transplantation (HSCT) patients. The study found associations with increased length of stay, ICU use, mortality, and costs, suggesting further research is needed.
Area of Science:
- Hematology
- Pediatric Oncology
- Transplantation Medicine
Background:
- Sinusoidal obstruction syndrome (SOS), or veno-occlusive disease, is a severe complication following hematopoietic stem cell transplantation (HSCT).
- Pediatric patients, especially those at high or very high risk, face significant risks from SOS.
- The efficacy of prophylactic defibrotide in preventing SOS remains uncertain, with limited U.S. data available.
Purpose of the Study:
- To evaluate the association of prophylactic defibrotide use with SOS incidence in pediatric HSCT.
- To assess the impact of prophylactic defibrotide on healthcare burden, including length of stay, ICU admissions, and costs.
- To examine the relationship between prophylactic defibrotide and patient outcomes such as mortality and acute graft-versus-host disease (GVHD).
Main Methods:
- A retrospective cohort study of 10,250 pediatric HSCT encounters using the Pediatric Health Information System.
- Patients were stratified into high-risk (n=9584) and very high-risk (n=666) groups based on HARMONY criteria.
- Outcomes including SOS incidence, length of stay (LOS), ICU admission, mortality, acute GVHD, and costs were analyzed using mixed-effects logistic regression.
Main Results:
- No statistically significant difference in SOS incidence was observed between prophylactic defibrotide and non-prophylaxis groups in either risk category.
- Patients receiving prophylactic defibrotide had longer median LOS, higher ICU admission rates, increased mortality, and greater healthcare costs.
- Acute GVHD incidence showed no significant differences, with conflicting trends between risk subgroups.
Conclusions:
- Prophylactic defibrotide use was not associated with a reduction in SOS incidence in this pediatric HSCT cohort.
- The findings suggest an association between prophylactic defibrotide and increased healthcare utilization, mortality, and costs.
- Residual confounding by indication is likely, necessitating prospective studies with robust confounding adjustment to clarify defibrotide's role in SOS prevention.
Abstract:
Background/Objectives: Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease, is a serious complication of hematopoietic stem cell transplantation (HSCT), particularly in high and very high-risk pediatric patients. Despite known risk factors, U.S. data remain limited. The benefit of prophylactic defibrotide is uncertain, with prior trials yielding inconclusive results. This study evaluates its use and association with SOS incidence, healthcare burden, and outcomes. Methods: We performed a retrospective cohort study of 10,250 pediatric HSCT encounters using the Pediatric Health Information System. Patients were stratified as high-risk (n = 9584) or very high-risk (n = 666) per HARMONY criteria. Prophylactic defibrotide was used in 344 encounters; 9906 received none (therapeutic use allowed after SOS diagnosis). Outcomes included SOS incidence, length of stay (LOS), ICU admission, mortality, acute GVHD, and costs. Mixed-effects logistic regression models with patients as a random intercept were used (p < 0.05). Results: SOS incidence differences between the defibrotide prophylaxis and non-prophylaxis groups were not statistically significant in either risk category (high-risk: 26% [n = 79/302] vs. 7.1% [n = 663/9282] p = 0.495, OR 1.457, 95% CI 0.494-4.296; very high-risk: 31.0% [n = 13/42] vs. 21.6% [n = 135/624], p = 0.970, OR 1.081, 95% CI 0.019-60.769). The extremely wide confidence intervals indicate that the data are consistent with both benefit and harm of prophylaxis. Median LOS was longer in the prophylactic group (40 vs. 33 days, p < 0.001; 56 vs. 49 days, p = 0.296, respectively). ICU admissions (50.7% vs. 32.8%; 69.0% vs. 50.8%), mortality (7.9% vs. 3.5%; 23.8% vs. 10.9%), and costs ($443,537 vs. $205,325; p < 0.001) were also higher in the prophylaxis group. Acute GVHD incidence differences were not statistically significant, with contradictory directions between risk subgroups. Conclusions: Prophylactic defibrotide was not associated with reduced SOS incidence and was associated with higher ICU use, longer LOS, increased mortality, and greater costs. These findings represent associations, not causation, and likely reflect residual confounding by indication-as defibrotide prophylaxis was preferentially administered to patients perceived to be at highest clinical risk. Prospective studies with appropriate confounding adjustment are needed to clarify the role of defibrotide in SOS prevention.