Defibrotide for prophylaxis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) in pediatric high-risk patients: consensus guidelines from the European Society for Blood and Marrow Transplantation (EBMT)
SOS/VOD is a life-threatening complication of hematopoietic stem cell transplantation, especially in children, with incidences reaching up to 15-20%. Despite efforts, SOS/VOD remains unpredictable with significant morbidity and mortality. High-risk criteria are clearly defined, and the pediatric EBMT diagnostic criteria have improved sensitivity, reducing treatment delays and enhancing outcomes. A meta-analysis combining retrospective and prospective studies found a risk ratio of 0.30 for SOS/VOD with defibrotide (DF) prophylaxis. Additionally, two prospective trials were conducted: the pediatric prevention trial (NCT00272948) and the Harmony Trial (NCT02851407), involving adults and children, with primary outcomes of incidence and SOS/VOD-free survival, respectively. The trials produced conflicting results regarding the effectiveness of prophylactic DF. Despite significant limitations of the Harmony trial, a direct healthcare professional communication (DHPC) from the European Medicines Agency (EMA) advised against prophylactic DF. This recommendation has serious consequences for children, especially infants, who are among the most vulnerable groups receiving HSCT. Therefore, a panel of experts issued guidelines for children at high risk for SOS/VOD, in which DF prophylaxis is considered justified. These guidelines include a weighted scoring system based on all relevant high-risk criteria to predict SOS/VOD, supporting decisions regarding the use of prophylactic DF in children.
Authors
- PG Richardson
- Fiona L. Dignan
- Heidrun Boztug
- Fabio Ciceri
- Kris Michael Mahadeo (ORCID: https://orcid.org/0000-0003-2649-9674)
- Antonio Colecchia (ORCID: https://orcid.org/0000-0002-8384-801X)
- Bülent Antmen (ORCID: https://orcid.org/0000-0001-6058-6021)
- Antonio Pagliuca (ORCID: https://orcid.org/0000-0003-2519-0333)
- Zofia Szmit (ORCID: https://orcid.org/0000-0002-1069-9404)
- Francesco Paolo Tambaro (ORCID: https://orcid.org/0000-0002-9145-3691)
- Elif ÜNAL İNCE
- Petr Sedláček (ORCID: https://orcid.org/0000-0001-7895-2886)
- Jerry Stein
- Akif Yeşilipek
- Krzysztof Kalwak
- Selim Corbacioglu
- Marco Zecca
- Marta Verna
- Rajinder Bajwa
- Peter J. Shaw
- Adriana Balduzzi
- Simone Cesaro
- Francesca Bonifazi
- Mohamad Mohty
- Katharina Kleinschmidt
Institutions
- University of Modena and Reggio Emilia (IT)
- Nationwide Children's Hospital (US)
- Memorial Sloan Kettering Cancer Center (US)
- Ankara University (TR)
- King's College - North Carolina (US)
- Duke University (US)
- Children's Hospital at Westmead (AU)
- University Hospital Regensburg (DE)
- Wroclaw Medical University (PL)
- Sorbonne Université (FR)
- Manchester University NHS Foundation Trust (GB)
- Azienda Ospedaliera Universitaria Integrata Verona (IT)
- Assistance Publique – Hôpitaux de Paris (FR)
- University Hospital in Motol (CZ)
- Hôpital Saint-Antoine (FR)
- Schneider Children's Medical Center (IL)
- Antalya Eğitim ve Araştırma Hastanesi (TR)
- Azienda Ospedaliera San Gerardo (IT)
- Dana-Farber Cancer Institute (US)
- Azienda USL di Bologna (IT)
- Santobono Children's Hospital (IT)
- IRCCS Ospedale San Raffaele (IT)
- Policlinico San Matteo Fondazione (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- King's College Hospital (GB)
- Antalya IVF (TR)
- University of Regensburg (DE)
- University of Milano-Bicocca (IT)
Publication Details
- Journal
- Bone Marrow Transplantation
- Published
- 2026-01-13
- DOI
- https://doi.org/10.1038/s41409-025-02793-x
- Citations
- 1
- Primary Topic
- Hematopoietic Stem Cell Transplantation
- Type
- article
- Field-Weighted Citation Impact
- 35.41