Hepatic veno-occlusive disease
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Talal Hilal, MD Mayo Clinic Phoenix, AZ, USA |
For placebo or observational studies in this condition, please visit this page.
Also known as sinusoidal obstructive syndrome (SOS)
Prophylaxis
Defibrotide monotherapy
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Corbacioglu et al. 2012 (VOD-DF) | 2006-2009 | Phase 3 (E-esc) | Observation | Seems to have lower incidence of VOD by day +30 (primary endpoint) |
| Grupp et al. 2023 (HARMONY) | 2017-01-11 to 2020-10-20 | Phase 3 (E-esc) | Best supportive care | Did not meet primary endpoint of VOD-free survival by day +30 |
Supportive therapy
- Defibrotide (Defitelio) 6.25 mg/kg IV over 2 hours every 6 hours
Begins on first day of preparative regimen, continues for at least 14 days or until day +30
References
- VOD-DF: Corbacioglu S, Cesaro S, Faraci M, Valteau-Couanet D, Gruhn B, Rovelli A, Boelens JJ, Hewitt A, Schrum J, Schulz AS, Müller I, Stein J, Wynn R, Greil J, Sykora KW, Matthes-Martin S, Führer M, O'Meara A, Toporski J, Sedlacek P, Schlegel PG, Ehlert K, Fasth A, Winiarski J, Arvidson J, Mauz-Körholz C, Ozsahin H, Schrauder A, Bader P, Massaro J, D'Agostino R, Hoyle M, Iacobelli M, Debatin KM, Peters C, Dini G. Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial. Lancet. 2012 Apr 7;379(9823):1301-9. Epub 2012 Feb 23. link to original article contains dosing details in manuscript PubMed NCT00272948
- HARMONY: Grupp SA, Corbacioglu S, Kang HJ, Teshima T, Khaw SL, Locatelli F, Maertens J, Stelljes M, Stepensky P, Lopez P, Amber V, Pagliuca A, Richardson PG, Mohty M. Defibrotide plus best standard of care compared with best standard of care alone for the prevention of sinusoidal obstruction syndrome (HARMONY): a randomised, multicentre, phase 3 trial. Lancet Haematol. 2023 May;10(5):e333-e345. Epub 2023 Mar 28. Erratum in: Lancet Haematol. 2023 Jul;10(7):e490. link to original article PubMed NCT02851407
Treatment
Defibrotide monotherapy
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Richardson et al. 2016 (DFCI 2005-01) | 2006-2008 | Phase 3 (E-esc) | "32 historical controls" | Seems to have superior survival at day +100 (primary endpoint) |
Note: If after 21 days signs and symptoms of VOD have not resolved, give until VOD is resolved, up to a maximum of 60 days.
Supportive therapy
- Defibrotide (Defitelio) 6.25 mg/kg IV over 2 hours every 6 hours
21- to 60-day course
References
- DFCI 2005-01: Richardson PG, Riches ML, Kernan NA, Brochstein JA, Mineishi S, Termuhlen AM, Arai S, Grupp SA, Guinan EC, Martin PL, Steinbach G, Krishnan A, Nemecek ER, Giralt S, Rodriguez T, Duerst R, Doyle J, Antin JH, Smith A, Lehmann L, Champlin R, Gillio A, Bajwa R, D'Agostino RB Sr, Massaro J, Warren D, Miloslavsky M, Hume RL, Iacobelli M, Nejadnik B, Hannah AL, Soiffer RJ. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. Blood. 2016 Mar 31;127(13):1656-65. Epub 2016 Jan 29. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00358501