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. 2019 Dec;54(12):1951-1962.
doi: 10.1038/s41409-019-0474-8. Epub 2019 Feb 25.

Systematic review of defibrotide studies in the treatment of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS)

Paul Richardson  1 , Saurabh Aggarwal  2 , Ozlem Topaloglu  3 , Kathleen F Villa  4 , Selim Corbacioglu  5
Affiliations

Systematic review of defibrotide studies in the treatment of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS)

Paul Richardson et al. Bone Marrow Transplant. 2019 Dec.

Erratum in

Abstract

Veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT) conditioning or high-dose nontransplant chemotherapy. VOD/SOS with multi-organ dysfunction (MOD) is associated with a mortality rate of > 80%. Defibrotide (25 mg/kg/day) is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post HSCT in the United States and to treat severe hepatic VOD/SOS in patients > 1 month of age in the European Union. A random effects model was used for pooling data from 17 systematically chosen defibrotide studies. For patients in these reports (n = 2598), and those in the subset of 10 reports of patients treated with ~ 25 mg/kg/day (n = 1691), estimated Day + 100 survival rates were 54% and 56%, respectively. Among those patients treated with ~ 25 mg/kg/day, estimated Day + 100 survival was 44% among patients with MOD and 71% in patients without MOD; survival was 41% and 70%, respectively, for the population of patients receiving any dose of defibrotide. Safety results were not pooled owing to differences in reporting methodology but were generally consistent with the known tolerability profile of defibrotide. This analysis provides the largest assessment of survival in patients treated with defibrotide for VOD/SOS with or without MOD.

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Conflict of interest statement

Paul G. Richardson has served on advisory committees and as a consultant, and received research funding from Jazz Pharmaceuticals. Saurabh Aggarwal and Ozlem Topaloglu are employees of Novel Health Strategies, which received funding from Jazz Pharmaceuticals for this analysis. Kathleen Villa is an employee of Jazz Pharmaceuticals and holds stock and/or stock options in Jazz Pharmaceuticals plc. Selim Corbacioglu has served as a consultant to and received honoraria from Gentium/Jazz Pharmaceuticals.

Figures

Fig. 1
Fig. 1
Study selection
Fig. 2
Fig. 2
Pooled analysis of the estimated Day + 100 survival rates of the overall patient populations treated with any defibrotide dose or ~ 25 mg/kg/day
Fig. 3
Fig. 3
Estimated Day + 100 survival for patients with MOD and without MOD
Fig. 4
Fig. 4
Estimated Day + 100 survival rates in pediatric and adult subgroups
See this image and copyright information in PMC

References

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