Preliminary Results from the North American Acute Promyelocytic Leukemia (APL) Study C9710.
Notice bibliographique
Résumé
Abstract This randomized phase III clinical trial was designed to evaluate the potential benefit and toxicity of giving two 25-day courses of arsenic trioxide as a first consolidation (0.15 mg/kg/d for 5d each wk for 5 wk) to half of newly diagnosed patients with APL who achieved remission (CR or PR) after induction with oral tretinoin (ATRA; 45 mg/m2/d), daunorubicin (50 mg/m2 IV × 4d), and cytarabine (200 mg/m2 CIV × 7d). Subsequent consolidation included 2 courses of ATRA (45 mg/m2 × 7d) + daunorubicin (50 mg/m2 × 3d; 2d for age < 15 yr) on both arms. CR patients were then randomized to 1 yr of maintenance with ATRA (7d repeated every other wk) with or without 6-mercaptopurine (daily) + methotrexate (wkly). 518 adults (15–79 yr) and 64 children (<15 yr; 11%) with untreated APL were enrolled by one of 5 cooperative groups (CALGB, ECOG, SWOG, COG, NCIC-CTG). Eligibility required demonstration of PML-RARA in one of 3 central labs. 52% were male; 73% were 15–60 yr old and 16% >60 yr old; 81% were white, 7% African American, 4% Hispanic, and 3% Asian. Performance status (PS) was 0 in 48%, 1 in 37%, 2 in 9%, and 3/4 in 6%. Body surface area (BSA) ranged from 0.37 to 3.19 m2. Results by treatment arm have not yet been released by the DSMB. There were 10 lethal adverse events among adults during induction that were either possibly, probably or definitely due to treatment; there were no lethal induction events among children. Maximum hematologic adverse events due to induction treatment were 7% grade (gr) 3 and 78% gr 4; maximum non-hematologic events due to treatment were 62% gr 3 and 23% gr 4. During consolidation therapy, there were no lethal events. Maximum hematologic adverse events due to treatment were 21% gr 3 and 58% gr 4 on the control arm, and 22% gr 3 and 54% gr 4 on the arsenic trioxide containing arm. Maximum non-hematologic adverse events due to consolidation treatment were 28% gr 3 and 5% gr 4 for the control arm and 43% gr 3 and 5% gr 4 for the arsenic trioxide containing arm. No gr 3/4 cardiac QTc prolongation was observed on the arsenic trioxide arm. Overall results confirm the validity of the European risk stratification scheme: Low (WBC ≤10,000 and platelets > 40,000); Intermediate (WBC ≤ 10,000 and platelets ≤40,000); High (WBC >10,000). Death during induction occurred in 2%, 4%, and 16%, respectively, in the 3 risk groups (p<0.0001). Among those who survived induction, relapses occurred within 1 yr in 2%, 3%, and 7%, respectively, by the same risk groups (p=0.07). Results were similar when only adult patients were analyzed (p=0.03 for relapse within first yr). The following factors had no significant relationship with death during induction or relapse within the first yr: PS, gender, extent of infection or bleeding at diagnosis, BSA, creatinine, hemoglobin, %CD56 positivity, and age. In conclusion, the induction, consolidation, and maintenance therapies evaluated in study C9710 were generally well tolerated overall and highly effective over the first year on study. High risk patients with WBC >10,000 require better therapy to reduce both induction mortality and early relapses. Reporting on differences between treatment arms on this trial must await more events and further follow-up.
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 | 0,001 | 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 ».