Incidence of Anicteric Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) and Efficacy of Defibrotide (DF) in Patients Post-HSCT in an Expanded-Access Program
Notice bibliographique
Résumé
IntroductionHepatic VOD/SOS is a progressive, potentially life-threatening complication of HSCT or nontransplant chemotherapy. VOD/SOS diagnosis by Baltimore criteria requires bilirubin >2 mg/dL; hyperbilirubinemia is not required by modified Seattle criteria, and may be a late finding in the progression of VOD/SOS. DF is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the US and Canada, and to treat severe hepatic VOD/SOS post-HSCT in patients (pts) aged >1 month in the EU. This post hoc analysis examines incidence of VOD/SOS without elevated bilirubin, and survival in DF-treated, post-HSCT pts in the expanded-access T-IND program (2007–2016).MethodsThe T-IND enrolled pts with VOD/SOS diagnosed per Baltimore or modified Seattle criteria. Patients received DF 25 mg/kg/day, recommended for ≥21 days.ResultsOf 991 post-HSCT pts with recorded bilirubin at diagnosis, 190 (19%) had bilirubin <2 mg/dL (Table). Of these, 133 were aged ≤16 years (24% of the 564 post-HSCT pediatric pts), and 57 were aged >16 years (13% of the 427 post-HSCT adults).Across all 1000 post-HSCT pts in the T-IND (including 9 without baseline bilirubin data), Kaplan-Meier estimated Day +100 survival (Figure) was 58.9% (95% CI, 55.7%–61.9%). In the overall population of pts with bilirubin <2 mg/dL, 61.1% and 18.4% of pts had ≥1 treatment emergent AE (TEAE) and ≥1 treatment related AE (TRAE), respectively, and 21.1% had ≥1 hemorrhage event; for pts with bilirubin ≥2 mg/dL: 73.8% had ≥1 TEAE, 21.7% had ≥1 TRAEs, and 31.1% had ≥1 hemorrhage event.ConclusionsIn the T-IND, 19% of post-HSCT pts with VOD/SOS had bilirubin <2 mg/dL at diagnosis (24% of children; 13% of adults). Accordingly, 190 pts would not have been diagnosed if hyperbilirubinemia was a required criterion. Of pts with bilirubin <2 mg/dL, 80% of pediatric pts and 49% of adults were diagnosed with VOD/SOS ≤21 days post-HSCT, showing that anicteric VOD/SOS can develop within 21 days post-HSCT in a considerable number of pediatric and adult pts. These results confirm that pediatric pts may not have hyperbilirubinemia, which is no longer mandatory for EBMT pediatric criteria, and further clearly show that anicteric VOD/SOS is also an adult phenotype. DF was associated with higher survival rate in pts with bilirubin <2 mg/dL compared with those with levels ≥2 mg/dL. These results compare favorably with the overall study findings, suggesting that treatment before the onset of hyperbilirubinemia may lead to better outcomes. The safety profile of the T-IND was similar to that of previous studies of DF for the treatment of VOD/SOS.SupportJazz Pharmaceuticals.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».