Safety and effectiveness of standard versus extended duration of anticoagulation in children with acute lymphoblastic leukemia and venous thrombo-embolism
Notice bibliographique
Résumé
Abstract Background Venous thrombo-embolism (VTE) occurs in up to 10% of pediatric patients with acute lymphoblastic leukemia (ALL). While anticoagulation is the mainstay of treatment, the optimal duration of therapeutic and/or prophylactic anticoagulation remains unclear. Aims To compare VTE progression/recurrence and bleeding rates based on duration of anticoagulation among pediatric patients treated for ALL with a history of central venous catheter (CVC)-related VTE, with duration of anticoagulation categorized as standard (i.e. until the end of asparaginase's expected effect or earlier) or extended (later than asparaginase's expected effect). Methods We performed a retrospective cohort study from three hospitals. Permission from the research ethics board was obtained at each institution. The cohort consisted of pediatric patients aged 1-21 years old with newly diagnosed ALL (2010-2023) receiving asparaginase-containing chemotherapy regimen who experienced a radiologically proven catheter-related VTE requiring medical intervention. Both symptomatic and clinically unsuspected VTEs were considered. The primary effectiveness outcome was time to VTE progression/recurrence. Safety outcomes were time to major bleeding and to clinically relevant non-major (CRNM) bleeding. All outcomes were defined using ISTH criteria (Mitchell, J Thromb Haemost, 2023). Asparaginase's expected effect was based on asparaginase formulation. Patients' characteristics are presented descriptively. We performed Cox proportional hazard models, with death considered a competing event, to compare rates of a) VTE progression/recurrence and b) CRNM bleeding, based on duration of anticoagulation. Results We included 109 patients (median age at ALL diagnosis: 9 years, interquartile range [IQR]: 4-13, 58% male) with ALL of B-cell (78%), T-cell (20%), or mixed/bilineage phenotype (2%). Most patients (104/109, 95%) received Dana-Farber Cancer Institute-based chemotherapy regimens. Patients had a median of 2 CVCs (IQR: 2-3); peripherally inserted central catheters were typically the first CVC (96/109, 88%) followed by totally implanted catheters as second CVC (57/88, 65%). Pegaspargase was the most common asparaginase used (91%). Index VTE occurred at a median of 75 days (IQR: 25-182) following ALL diagnosis. Anticoagulation was used in 106/109 (97%) of patients. The preferred initial agent was enoxaparin (101/106, 95%) and median duration of anticoagulation was 6.4 months (IQR: 3.2-9.5). Anticoagulation was stopped before and after the end of asparaginase's expected effect in 46 (43%) and 40 (38%) of patients, respectively, while 20 patients (19%) had extended anticoagulation, typically until CVC removal. Overall, 19 patients (17%) sustained a VTE recurrence/progression, at a median of 63 days (IQR: 32-280) following index VTE. Eight events were progression (5/8 symptomatic, all while on anticoagulation), and 11 were recurrences (7/11 symptomatic, 7/11 while on anticoagulation). Of 15 patients on anticoagulation at time of VTE recurrence/progression, 10 were receiving therapeutic doses and 5 were receiving prophylactic doses. Duration of anticoagulation did not predict VTE recurrence/progression (extended vs. standard: HR: 1.76, 95% CI: 0.57-5.39, p=0.323). Major bleed was rare, occurring in 3 (2.8%) patients. Two major bleeds were intracranial hemorrhage occurring within the first week of therapeutic anticoagulation in patients with systemic fungal infections; one was an intracranial bleeding following a stroke. CRNM bleed occurred in 2/20 patients on extended anticoagulation and 3/86 patients on standard anticoagulation (HR: 3.01, 95% CI: 0.55-16.60, p=0.205).Conclusions: VTE progression/recurrence following a first VTE occurred in 17% of children and adolescents with ALL. In this retrospective analysis, extended anticoagulation was not associated with a reduced risk of VTE progression/recurrence. This could suggest that an extended anticoagulation approach is not more effective or could reflect confounding by indication where patients considered at higher risk of progression/recurrence received longer antithrombotic treatment. Overall, in our cohort, the risk of VTE progression/recurrence appeared higher than the risk of major and/or CRNM bleeding. Further investigation into alternative approaches to reduce VTE progression/recurrence is warranted in children and adolescents with ALL receiving asparaginase-containing regimens.
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,008 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 source (Gemma direct ou Codex distillé), 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 ».