System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Ahead of print

PubMed: 41530538 DOI: 10.1038/s41409-025-02793-x

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).

Bone Marrow Transplant

Authors: Selim Corbacioglu, Rajinder Bajwa, Ali Bülent Antmen, Adriana Balduzzi, Jaap Jan Boelens, Francesca Bonifazi, Simone Cesaro, Fabio Ciceri, Antonio Colecchia, Fiona Dignan, Katharina Kleinschmidt, Kris M Mahadeo, Antonio Pagliuca, Petr Sedlacek, Peter J Shaw, Jerry Stein, Zofia Szmit, Francesco Tambaro, Elif Ince, Marta Verna, Akif Yesilipek, Marco Zecca, Paul G Richardson, Mohamad Mohty, Krzysztof Kalwak

Affiliations

  • Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany.
  • Division of Hematology/Oncology/BMT, Nationwide Children's Hospital, Columbus, OH, USA.
  • Pediatric Hematology and Stem Cell Transplantation Unit, Acıbadem Adana Hospital, Adana, Turkey.
  • Hematopoietic Stem Cell Transplant Unit, Department of Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
  • School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
  • Department of Pediatrics, Transplantation and Cellular Therapies Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • IRCCS Azienda Ospedaliera-Universitaria di Bologna, Bologna, Italy.
  • Pediatric Hematology Oncology, Department of the Mother and Child, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
  • Hematology and Bone Marrow Transplantation Unit, IRCCS Ospedale San Raffaele, University Vita-Salute, Milano, Italy.
  • Gastroenterology Unit, CHIMOMO Department, University of Modena and Reggio Emilia, Modena, Italy.
  • Manchester University NHS Foundation Trust, Manchester, UK.
  • Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany.
  • Pediatric Transplant and Cellular Therapy, Duke University, Durham, NC, USA.
  • Department of Hematological Medicine, King's College Hospital & Kings College London, London, UK.
  • Department of Pediatric Hematology and Oncology Teaching Hospital Motol, 2nd Medical School, Charles University Motol, Prague, Czechia.
  • Blood Transplant and Cell Therapies Program, The Children's Hospital, Westmead, NSW, Australia.
  • Schneider Children's Medical Center of Israel and Sackler Faculty of Medicine, University of Tel Aviv, Tel Aviv, Israel.
  • Clinical Department of Pediatric BMT, Oncology and Hematology, Wroclaw Medical University, Wroclaw, Poland.
  • Stem Cell Transplantation and Cell Therapy Division-AORN Santobono Pausilipon, Napoli, Italy.
  • Division of Pediatric Hematology Oncology and Stem Cell Transplantation, Ankara University Faculty of Medicine, Ankara, Turkey.
  • Pediatric Hematology and Stem Cell Transplantation Unit, Medicalpark Antalya Hospital, Antalya, Turkey.
  • Fondazione IRCCS Policlinico San Matteo Pediatric Hematology-Oncology, Pavia, Italy.
  • Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA.
  • Hematology Department, AP-HP, Hôpital Saint-Antoine, Sorbonne Université, Paris, France.

Abstract

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.

MeSH

Hepatic Veno-Occlusive Disease, Blood, Microscopy, Electron, Scanning Transmission, Incidence, Transplantation, Child