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) - Report - MDSpire
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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)
EBMT Guidelines on Defibrotide for Preventing SOS/VOD in High-Risk Pediatric Patients
Overview
Sinusoidal obstruction syndrome (SOS/VOD) is a severe early complication post-hematopoietic stem cell transplantation in children, with incidences historically exceeding 15-20%. The European Society for Blood and Marrow Transplantation (EBMT) has issued pediatric-specific diagnostic criteria and recommends defibrotide prophylaxis to reduce morbidity and mortality in high-risk pediatric patients.
Background
SOS/VOD is characterized by hepatic sinusoidal and venular injury leading to liver failure and multi-organ dysfunction. Pediatric patients exhibit higher incidence rates and unique clinical presentations, including a significant proportion with anicteric SOS/VOD, complicating diagnosis. Traditional diagnostic criteria relying on hyperbilirubinemia may miss early or anicteric cases, prompting the development of the pEBMT criteria incorporating transfusion-refractory thrombocytopenia (tRT) as an early marker. Defibrotide, targeting endothelial injury, has emerged as a promising prophylactic and therapeutic agent.
Data Highlights
Parameter
Incidence/Rate
Average SOS/VOD incidence in children
15-20% (historically up to 60%)
Average SOS/VOD incidence in adults
<10%
Anicteric SOS/VOD prevalence
Up to 30%
Risk ratio for SOS/VOD with defibrotide prophylaxis (meta-analysis)
0.30 (95% CI)
Incidence of SOS/VOD without elevated bilirubin (T-IND trial)
23% overall; 29% children; 15% adults
Key Findings
Children have a substantially higher incidence of SOS/VOD compared to adults, with rates historically reaching up to 60%.
Anicteric SOS/VOD, lacking hyperbilirubinemia, occurs in up to 30% of cases, challenging traditional diagnostic criteria.
The pEBMT diagnostic criteria incorporate transfusion-refractory thrombocytopenia (tRT) as an early and sensitive marker for pediatric SOS/VOD.
Defibrotide prophylaxis significantly reduces the risk of SOS/VOD, with a risk ratio of approximately 0.30 in meta-analyses.
Early diagnosis and intervention, prior to the onset of hyperbilirubinemia, improve outcomes and reduce mortality in pediatric patients.
Clinicians should apply the pEBMT criteria for early detection of SOS/VOD in pediatric patients, emphasizing transfusion-refractory thrombocytopenia as a key early sign. Prophylactic use of defibrotide in high-risk children is recommended to prevent SOS/VOD and improve survival outcomes. Awareness of anicteric presentations is critical to avoid delayed diagnosis and treatment.
Conclusion
The EBMT guidelines underscore the importance of pediatric-specific diagnostic criteria and the prophylactic use of defibrotide to mitigate the high burden of SOS/VOD in children undergoing hematopoietic stem cell transplantation. Early recognition and intervention remain pivotal to improving prognosis.
References
Corbacioglu et al. BMT 2018 -- Pediatric SOS/VOD Diagnostic Criteria
McDonald et al. 1993 -- Transfusion-Refractory Thrombocytopenia in SOS/VOD
T-IND Trial NCT00628498 -- Incidence and Outcomes of SOS/VOD
EBMT Guidelines 2018 -- Defibrotide Use in Pediatric SOS/VOD
by 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
