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)
Corbacioglu S, Bajwa R, Antmen AB, Balduzzi A, Boelens JJ, Bonifazi F, Cesaro S, Ciceri F, Colecchia A, Dignan F, Kleinschmidt K, Mahadeo KM, Pagliuca A, Sedlacek P, Shaw PJ, Stein J, Szmit Z, Tambaro F, Ince E, Verna M, Yesilipek A, Zecca M, Richardson PG, Mohty M, Kalwak K (2026) · Bone Marrow Transplantation · n=0
Studienprofil
- Design
- EBMT pediatric expert consensus guidelines synthesizing meta-analytic evidence (RR 0.30 for defibrotide prophylaxis) and two prospective trials (NCT00272948 pediatric prevention, NCT02851407 Harmony Trial)
- Stichprobengröße (n)
- —
- Intervention
- Defibrotide prophylaxis for pediatric hematopoietic stem cell transplant patients at high risk of sinusoidal obstruction syndrome/veno-occlusive disease
- Komparator
- No prophylaxis (EMA Direct Healthcare Professional Communication had advised against prophylactic use)
- Primärer Endpunkt
- Consensus weighted scoring system for SOS/VOD risk prediction and prophylaxis decision-making
- Primäres Ergebnis
- Meta-analysis combining retrospective and prospective studies found RR 0.30 for SOS/VOD with defibrotide prophylaxis; expert panel recommends prophylaxis is justified in pediatric high-risk patients despite conflicting Harmony Trial results and EMA DHPC advisory
- Follow-up-Dauer
- 100-day post-HSCT (typical VOD onset window)
- PMID
- 41530538
Wichtigste Ergebnisse
- RR 0.30 for SOS/VOD with defibrotide prophylaxis from combined meta-analysis
- EMA Direct Healthcare Professional Communication advised against prophylactic use
- Expert panel reaches contrary conclusion for pediatric high-risk patients
- Weighted scoring system developed for individualized decision-making
- Highlights regulatory-clinical evidence tension
Einschränkungen
- Conflicting prospective trial results (NCT00272948 vs Harmony Trial)
- Harmony Trial methodologic limitations
- EMA DHPC advisory creates regulatory uncertainty
- Pediatric infant subgroup most affected by access decisions
- Not applicable to whole-leech hirudotherapy
Klinische Implikationen
Corbacioglu 2026 illustrates how expert consensus can responsibly diverge from regulatory advisories when underlying evidence justifies. For ASH, this EBMT pediatric guideline exemplifies the structural complexity of the defibrotide pharmaceutical pathway operating under both regulatory tension and meta-analytic support. The K040187 device-leech US clinical practice operates without analogous prophylactic-indication regulatory uncertainty.
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Burden of illness of non-hematopoietic stem cell transplant-related hepatic sinusoidal obstruction syndrome: A systematic review
Fan L, Stewart F, Ruiz K, Devani D, Fusco N, Gill M, Amber V, Su W, Gangi A, Hanvesakul R (2024)
Hepatic Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease (SOS/VOD) Primary Prophylaxis in Patients Undergoing Hematopoietic Stem Cell Transplantation: A Network Meta-Analysis of Randomized Controlled Trials
Sousa-Pimenta M, Martins Â, Estevinho LM, Pinho Vaz C, Leite L, Mariz J (2024)
Impact of Oral Eicosapentaenoic Acid on Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome Onset Prevention: Single-Center Retrospective Analysis
Miyazaki Y, Narumi H, Azuma T, Tanimoto K, Masuda Y, Kato J, Konishi T, Nabe S, Maruta M, Ochi T, Yamanouchi J, Takenaka K (2025)