Combination of Dexamethasone and Asparaginase Induces Prothrombotic State in Children Receiving Multiagent Chemotherapy for Acute Lymphoblastic Leukemia
Notice bibliographique
Résumé
Abstract Abstract 3536 Background: Concomitant administration of asparaginase (ASP) and steroids, backbone of front line acute lymphoblastic leukemia (ALL) therapy, are shown to increase the risk of thromboembolism (TE). On Dana-Farber Cancer Institute (DFCI) ALL Consortium studies occurrence of TE is frequent during ASP intensification phase where pulse steroids are administered for 5 days at the start of a 3-week multiagent chemotherapy cycle (Grace et al, 2011). The DFCI ALL 05–001 trial randomized children to PEG ASP (2500IU/m2 intravenous every 14 days) or E. coli ASP (25000 IU/m2 intramuscular every 7 days) for 30 weeks. Aims: We undertook an exploratory study to investigate changes in hemostatic factors from baseline to after administration of ASP with and without dexamethasone (Dex) (standard risk: 6mg/m 2/day, high risk: 18mg/m 2/day × 5 days), and the influence of type of ASP, if any, in children receiving consolidation II therapy on the 05–001 protocol. Methods: Children (>1 to ≤18 years of age) in remission following consolidation I therapy, with no history of TE or allergy to ASP, were eligible to participate. Blood samples were collected at 3 time points: prior to the first post-induction dose of ASP (“baseline”), at a week 2 (effects of ASP and Dex therapy) and prior to subsequent week 1 (effect of ASP only). Samples were analyzed for procoagulant factors [F VIII:C, vonWillebrand Factor (vWF) antigen], markers of natural anticoagulant factors [antithrombin (AT), protein C (PC), free protein S (PS)], fibrinolytic proteins [plasminogen, tissue plasminogen activator antigen (tPA-Ag), plasminogen activator inhibitor-1antigen (PAI-1Ag), D-Dimer] and endogenous thrombin generation [prothrombin activation fragment (F1.2)]. Baseline parameters were compared to parameters after ASP and Dex therapy, and after ASP only therapy, using paired t-tests. Change in parameters were also compared for patients receiving PEG versus E coli ASP using Student's t-test. Results: Of the 20 participants (mean age of 5.8 years; 11 male; 5 high risk), 10 were randomized to PEG ASP. Although significant reduction in AT and PS occurred following ASP alone therapy, the values were within normal range. Type of ASP had no effect on hemostatic parameters except protein S (significant reduction) and PAI-1 Ag (significant increase) in patients treated with PEG ASP compared to E. coli ASP. Compared to baseline FVIII and vWF were significantly increased only after ASP-Dex therapy (Table 1). D-dimer and plasminogen decreased with ASP-Dex and ASP only therapy. There was significant increase in F1.2 following ASP therapy, but more so after ASP-Dex therapy. Limitations: Small sample size and exploratory, single institution study, undertaken within the context of multi-agent chemotherapy, are limitations of this study. Conclusion: Concomitant Dex and ASP, administered in conjunction with multiagent chemotherapy, induces prothrombotic state compared to baseline or that following ASP alone, with resultant increases in procoagulant factors (FVIII, vWF), reduction in fibrinolytic potential as indicated by decrease in plasminogen and D-Dimer, and increase in endogenous thrombin generation reflected by increase in F1.2. This may explain clinical observations of increased prevalence of TE in patients receiving concomitant ASP and steroids. Disclosures: No relevant conflicts of interest to declare.
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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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| 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 | 0,001 |
| 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 ».