Long Term Follow-Up of a Randomized Trial Comparing Response Adapted (RA), Non-Cross Resistant Induction and Consolidation with Idarubicin/Cytarabine (IDAC) Followed by Mitoxantone/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: Previously the CLSG studied response adapted rx (RA) using idarubicin 12mg/m2 d1-3/cytarabine 200mg/m2 d1-7(IDAC); followed by IDAC and mitoxantrone 10mg/m2/etoposide 100mg/2 d1-5(NOVE) if in CR afer IDAC, or NOVEx2 if they had persistent blasts at d 14 or on recovery. The 10 year follow-up demonstrated that RA rx appeared to have an encouraging response and lead to longer survival. We elected to compare consolidation with RA vs high dose ara-c(HDAC). Methods: Pts. with newly dx’d AML were included who were: age 15–80, with ECOG performance status 0–2, with no hx of HIV, CML or MDS>3 mos, and had bilirubin<85mmol/l(5.0mg/dl), creatinine<220 mmol/l(2.2mg/dl), no previous chemorx or radiorx for another malignancy, and an ejection fraction≥40%. Pts were given induction with (IDAC). Pts with persistent marrow blasts at d14, or after recovery, were given (NOVE). Pts in CR were randomized to obtain consolidation rx with: either IDAC followed by NOVE-arm A, or HDACx2-arm B, and if they required NOVE to obtain CR, HDACx2-arm C, or NOVEx2-arm D. HDAC was given at a 3 gms/m2 q12h on days 1,3,5 if pts were ≤ 60 and 1gm/m2 on days 1,3,5 if>60. Dosage adjustments were made to idarubicin according to bilirubin, to etoposide according to AST, and to HDAC according to ALP and creatinine. Pts with M3 were rx’d with ATRA x45d after achieving CR, prior to consolidation. Pts. were stratified according to age and # of inductions required to achieve CR, and were followed for death, relapse, or BMT. All pts were followed until death. Pts were also followed for quality of life using the SF-36 and FLIC surveys which pts completed at baseline,1,4, and 12 mos post rx. Data was analysed by an independent data monitoring committee comprised of a non-blinded statistician, and hematologist and oncologist not participating in the study who were blinded to rx allocation. Analyses was done on intent-to-rx basis using the group sequential design with early stopping boundaries. Survival was summarized using Kaplan-Meier curves and comparisons were made using the log rank test. Results: 503 pts were recruited from 5/96 until 12/01 of whom 461were assessable and 296 were randomized. 201 pts were age≤60 and 95 were>60. Median follow-up since randomization was 64 mos. Comparing RA(arms A+D) vs HDAC(armsC+D), DFS in pts<60 was 32 vs. 23 mos(p=.46) and median OS was not yet reached vs.60 mos(p=.46). Median DFS in RA pts>60 was 20 vs.13 mos following HDAC(p=.15). For those pts >60 disease free at 6 mos, median DFS was 27 mos after RA vs.10 mos post HDAC(p=.05). There was a trend towards higher mortality in BMT patients <60, following HDAC, as the DFS post BMT in RA pts was 36 mos vs.17 mos post HDAC(p=.16). D14 marrow was a significant predictor of both DFS and OS in all pts (p=.0001). Conclusion: This study suggests that RA consolidation is advantageous over HDAC, particularly in patients >60 and in those <60 who get a BMT. Thus in the next CLSG trial, RA rx has been adopted as standard rx in pts>60.
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 | 0,004 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,003 | 0,003 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,002 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,005 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 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 ».