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)

Selim Corbacioglu¹, Rajinder Bajwa², Ali Bülent Antmen³, Adriana Balduzzi^{4

5}, Jaap Jan Boelens⁶, Francesca Bonifazi⁷, Simone Cesaro⁸, Fabio Ciceri⁹, Antonio Colecchia¹⁰, Fiona Dignan¹¹, Katharina Kleinschmidt¹², Kris M Mahadeo¹³, Antonio Pagliuca¹⁴, Petr Sedlacek¹⁵, Peter J Shaw¹⁶, Jerry Stein¹⁷, Zofia Szmit¹⁸, Francesco Tambaro¹⁹, Elif Ince²⁰, Marta Verna⁴, Akif Yesilipek²¹, Marco Zecca²², Paul G Richardson²³, Mohamad Mohty²⁴, Krzysztof Kalwak¹⁸; EBMT Paediatric Diseases Working Party

Affiliations

¹ Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany. selim.corbacioglu@ukr.de.
² Division of Hematology/Oncology/BMT, Nationwide Children's Hospital, Columbus, OH, USA.
³ Pediatric Hematology and Stem Cell Transplantation Unit, Acıbadem Adana Hospital, Adana, Turkey.
⁴ Hematopoietic Stem Cell Transplant Unit, Department of Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
⁵ School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
⁶ Department of Pediatrics, Transplantation and Cellular Therapies Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁷ IRCCS Azienda Ospedaliera-Universitaria di Bologna, Bologna, Italy.
⁸ Pediatric Hematology Oncology, Department of the Mother and Child, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
⁹ Hematology and Bone Marrow Transplantation Unit, IRCCS Ospedale San Raffaele, University Vita-Salute, Milano, Italy.
¹⁰ Gastroenterology Unit, CHIMOMO Department, University of Modena and Reggio Emilia, Modena, Italy.
¹¹ Manchester University NHS Foundation Trust, Manchester, UK.
¹² Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany.
¹³ Pediatric Transplant and Cellular Therapy, Duke University, Durham, NC, USA.
¹⁴ Department of Hematological Medicine, King's College Hospital & Kings College London, London, UK.
¹⁵ Department of Pediatric Hematology and Oncology Teaching Hospital Motol, 2nd Medical School, Charles University Motol, Prague, Czechia.
¹⁶ Blood Transplant and Cell Therapies Program, The Children's Hospital, Westmead, NSW, Australia.
¹⁷ Schneider Children's Medical Center of Israel and Sackler Faculty of Medicine, University of Tel Aviv, Tel Aviv, Israel.
¹⁸ Clinical Department of Pediatric BMT, Oncology and Hematology, Wroclaw Medical University, Wroclaw, Poland.
¹⁹ Stem Cell Transplantation and Cell Therapy Division-AORN Santobono Pausilipon, Napoli, Italy.
²⁰ Division of Pediatric Hematology Oncology and Stem Cell Transplantation, Ankara University Faculty of Medicine, Ankara, Turkey.
²¹ Pediatric Hematology and Stem Cell Transplantation Unit, Medicalpark Antalya Hospital, Antalya, Turkey.
²² Fondazione IRCCS Policlinico San Matteo Pediatric Hematology-Oncology, Pavia, Italy.
²³ Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA.
²⁴ Hematology Department, AP-HP, Hôpital Saint-Antoine, Sorbonne Université, Paris, France.

PMID: 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)

Selim Corbacioglu et al. Bone Marrow Transplant. 2026.

. 2026 Jan 13.

doi: 10.1038/s41409-025-02793-x. Online ahead of print.

Authors

Affiliations

¹ Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany. selim.corbacioglu@ukr.de.
² Division of Hematology/Oncology/BMT, Nationwide Children's Hospital, Columbus, OH, USA.
³ Pediatric Hematology and Stem Cell Transplantation Unit, Acıbadem Adana Hospital, Adana, Turkey.
⁴ Hematopoietic Stem Cell Transplant Unit, Department of Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
⁵ School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
⁶ Department of Pediatrics, Transplantation and Cellular Therapies Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁷ IRCCS Azienda Ospedaliera-Universitaria di Bologna, Bologna, Italy.
⁸ Pediatric Hematology Oncology, Department of the Mother and Child, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
⁹ Hematology and Bone Marrow Transplantation Unit, IRCCS Ospedale San Raffaele, University Vita-Salute, Milano, Italy.
¹⁰ Gastroenterology Unit, CHIMOMO Department, University of Modena and Reggio Emilia, Modena, Italy.
¹¹ Manchester University NHS Foundation Trust, Manchester, UK.
¹² Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany.
¹³ Pediatric Transplant and Cellular Therapy, Duke University, Durham, NC, USA.
¹⁴ Department of Hematological Medicine, King's College Hospital & Kings College London, London, UK.
¹⁵ Department of Pediatric Hematology and Oncology Teaching Hospital Motol, 2nd Medical School, Charles University Motol, Prague, Czechia.
¹⁶ Blood Transplant and Cell Therapies Program, The Children's Hospital, Westmead, NSW, Australia.
¹⁷ Schneider Children's Medical Center of Israel and Sackler Faculty of Medicine, University of Tel Aviv, Tel Aviv, Israel.
¹⁸ Clinical Department of Pediatric BMT, Oncology and Hematology, Wroclaw Medical University, Wroclaw, Poland.
¹⁹ Stem Cell Transplantation and Cell Therapy Division-AORN Santobono Pausilipon, Napoli, Italy.
²⁰ Division of Pediatric Hematology Oncology and Stem Cell Transplantation, Ankara University Faculty of Medicine, Ankara, Turkey.
²¹ Pediatric Hematology and Stem Cell Transplantation Unit, Medicalpark Antalya Hospital, Antalya, Turkey.
²² Fondazione IRCCS Policlinico San Matteo Pediatric Hematology-Oncology, Pavia, Italy.
²³ Department of Medical Oncology, Dana-Farber Cancer Institute, Jerome Lipper Center for Multiple Myeloma Research, Harvard Medical School, Boston, MA, USA.
²⁴ Hematology Department, AP-HP, Hôpital Saint-Antoine, Sorbonne Université, Paris, France.

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

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.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

1. Kleinschmidt K, Troeger A, Foll J, Hanafee-Alali T, Jakob M, Kramer S, et al. Defibrotide for the treatment of veno-occlusive disease/sinusoidal obstruction syndrome in paediatric patients who did not receive haematopoietic stem cell transplantation: case reports of patients from a German academic hospital. EJHaem. 2025;6:e1094. https://doi.org/10.1002/jha2.1094 . - DOI - PubMed - PMC
1. Esposto MP, Milani E, Tridello G, Caddeo G, Bonetti E, Pezzella V et al. Hepatic veno-occlusive disease (VOD) as a complication of hematopoietic stem cell transplantation (HSCT) or after chemotherapy alone in the pediatric population: a single-center experience. In: Proceedings of the EHA 2025 Congress. Milan, Italy: European Hematology Association; 2025.
1. Escribano-Serrat S, Rodríguez-Lobato LG, Charry P, Martínez-Cibrian N, Suárez-Lledó M, Rivero A, et al. Endothelial activation and stress index in adults undergoing allogeneic hematopoietic cell transplantation with post-transplant cyclophosphamide-based prophylaxis. Cytotherapy. 2024;26:73–80. https://doi.org/10.1016/j.jcyt.2023.10.008 . - DOI - PubMed
1. Balaguer-Roselló A, Montoro J, Villalba M, Lizama P, Torres L, Chorão P et al. Sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation with post-transplant cyclophosphamide. Transplant Cell Ther 2025 https://doi.org/10.1016/j.jtct.2025.05.018 .
1. Locatelli F, Lang P, Wall D, Meisel R, Corbacioglu S, Li AM, et al. Exagamglogene autotemcel for transfusion-dependent beta-thalassemia. N Engl J Med. 2024;390:1663–76. https://doi.org/10.1056/NEJMoa2309673 . - DOI - PubMed

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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)

Affiliations

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)

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous