A Multicenter Randomized Trial Comparing Response-Adapted (RA), Non-Cross-Resistant Induction and Consolidation with Idarubicin/Cytarabine (IDAC) Followed by Mitoxantrone/Etoposide (NOVE) Compared with Consolidation with High Dose Cytarabine (HDAC) in Adult Patients with AML. A Study by the Canadian Leukemia Studies Group (CLSG).
Notice bibliographique
Résumé
Abstract Background: A CLSG pilot rx’d 140 pts.with Response Adapted Rx(RA) with Idarubicin 12 mg/m2 d1-3 & Ara-C 200 mg/m2 d1-7(IDAC);followed by IDAC II, then Mitoxantrone10 mg/m2&VP-16 100 mg/m2d1-5(NOVE), if in CR after IDAC, & NOVE x2 if they had persistent blasts @ d14 or @ recovery. CR rate was 74% in pts age15–80.DFS and OS were favourable @ 20 mos & 47 mos in pts ≤ 60. A CALGB study demonstrated the advantage of consolidation with high dose Ara-C(HDAC).We chose to compare HDAC with RA. Methods: All pts with AML, age15–80, with a performance of 0–2,were included except those with a hx of MDS>3 mos,bili>85 mmol/l, creatinine>220 mmol/l, hx of chemoRx or radiation Rx for another malignancy,CML, ejection fraction<40%,or HIV+. Pts were randomized in CR to obtain consolidation Rx with: either IDAC followed by NOVE - Arm A, or 2 cycles of HDAC as given by the CALGB-Arm B, and if they required NOVE to obtain CR-2 cycles of HDAC-Arm C, or 2 cycles of NOVE - Arm D. HDAC was given at 3 g/m2 if pts were ≤ 60 and 1 g/m2 if >60. Dosage adjustments were made to VP-16 according to ↑ AST, to Idarubicin according to↑ bilirubin, and to HDAC according to ↑ ALP and/or ↑ creatinine. Pts with M3 were to be treated at least 45 days with ATRA. Pts were stratified according to age and # of inductions required to achieve CR and were followed until death, relapse, or BMT. Pts were followed for quality of life using both the SF-36 and the FLIC surveys which pts completed at baseline,1,4 and 12 mos post discharge from consolidation. Data went through annual analyses by an independent data monitoring committee comprised of a non-blinded statistician, a hematologist, and a an oncologist not participating in the study who were blinded to treatment allocation. Their analysis was done using group sequential design with early stopping boundaries. Results: The comparison was made between the RA approach (Arms A+D) vs. consolidation with HDAC (Arms B+C). Analysis was done on an intent-to-treat basis. 503 patients were recruited into the study from 5/96 until 12/01, of whom 461 were assessable. 201 age ≤ 60 and 95 age > 60 were randomized with a median time since randomization of 65.7 mos.Median DFS in RA pts > 60 was 20 mos vs. 13.3 mos in the HDAC arm (p=.15). The overall DFS hazard ratio was 0.72 (0.47, 1.13), p=0.153. For those RA pts > 60 and disease free at 6 mos, the median DFS was 27.3 mos vs. 10.2 mos in the HDAC arm with the hazard ratio of 0.57 (0.33, 1.02), p=0.056. Median DFS in pts ≤ 60 was 32 mos in pts randomized to RA and was 22.8 mos in the HDAC arm. Median OS in pts ≤ 60 has not yet been reached in pts randomized to RA and was 60.2 mos in the HDAC arm. In the RA pts > 60 the median OS was 21.1 mos vs. 19 mos in the HDAC arm. Notably, there is a trend in 117 pts ≤ 60 undergoing BMT to have lower mortality if treated with RA 21 (41.2%), rather than with HDAC 37 (56.1%), p=0.11. Conclusion: Although this study was not sufficiently powered to detect a statistically significant difference at the 0.05 level it suggests that RA therapy is advantageous over HDAC consolidation therapy, particularly for pts > 60 and for those who may get a BMT.
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 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,003 | 0,003 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,002 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,004 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,001 |
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 ».