A Multicenter Phase II Study Using a Dose Intensified Pediatric Regimen in Adults with Untreated Acute Lymphoblastic Leukemia.
Notice bibliographique
Résumé
Abstract Background: Current chemotherapy regimens in children with ALL produce event-free survival (EFS) rates of greater than 80%. In contrast, adults with ALL have a much poorer prognosis, with EFS rates of 30–40%. Recent retrospective studies suggest that young adults may have superior outcomes when treated with intensive pediatric regimens. Unfortunately, prospective studies are lacking. This phase II trial was performed to determine if an intensive pediatric regimen could be administered to adults with ALL. Methods: The therapeutic backbone of this protocol is based on the high-risk arm of the DFCI Childhood ALL Consortium Protocol 00-01. Patients with newly diagnosed ALL received induction chemotherapy, which included doxorubicin, prednisone, vincristine, high-dose methotrexate, L-asparaginase (L-asp), and triple intrathecal therapy. CNS prophylaxis included triple intrathecal therapy and cranial radiation. Intensification therapy consisted of ten 3-week courses of doxorubicin, vincristine, dexamethasone, 6-mercaptopurine and 30 weeks of L-asp that was dosed to maintain asparagine depletion, defined as an L-asp level between 0.1 and 0.14. Continuation therapy consisted of 3 week courses of vincristine, dexamethasone, methotrexate and 6-mercaptopurine for a total of 2 years from an established complete remission (CR). Results: 89 patients have been enrolled and treated to date. The first 75 eligible patients were used for this analysis, 73 of whom had on-study data. Although there was no initial upper age restriction, the protocol was amended to include only patients between the ages of 18–50 with de novo ALL, which excluded 4 patients from the analysis. The median age was 28 years, (range, 18–50), 60% were male, 74% had B-lineage phenotype, and 20% were Philadelphia chromosome positive. The CR rate after 4 weeks was 84%. 39 patients had the opportunity to complete L-asp intensification therapy, and 27 (69%) completed all 30 weeks. The median L-asp dose was 16,582 U/m2 (starting dose was 12,500 U/m2). One death occurred during induction therapy (sepsis). Nine patients developed pancreatitis, one of whom died. This last case represented the only remission death on study. Two patients developed osteonecrosis, 14 thrombosis/embolism and 23 neutropenic infection during the post-remission period. With a median follow-up time of 15.3 months, the estimated 2-yr EFS is 72.5% (95%CI: 61–84%) and the estimated 2-yr overall survival (OS) is 77.1% (95%CI: 67–95%). Conclusions: The administration of a dose intensified pediatric regimen to adults with ALL is feasible. Although the high EFS and OS rates require longer follow up, such intensive treatment strategies for young adults with ALL could represent a major therapeutic advance.
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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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,002 |
| 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.
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