Predictive Value of Molecular Remissions Post Consolidation Chemotherapy in Patients with Core Binding Factor (CBF) Acute Myeloid Leukemias – a Single Centre Analysis
Notice bibliographique
Résumé
Abstract Background: Acute myeloid leukemia (AML) with t(8;21) or inv(16) is commonly referred to as core-binding factor AML (CBF-AML). Although this group represents a favorable cytogenetic AML subgroup, 30-40% of these patients nevertheless relapse after standard intensive chemotherapy. The incorporation of high-dose cytarabine for postremission therapy has substantially improved the outcome of CBF-AML patients, especially when administered as 2-4 repetitive cycles. Here we present retrospective data from a single centre, on this favourable AML subgroup. Methods: We analyzed retrospectively the outcome of 80 sequential patients with CBF-AML (46 t(8;21), 34 inv(16)/t(16;16)) treated over a 13 year period from 2000-2012. The median age was 48 years (range 20-80) with a median white cell count of 13x109/L(range 1-426x109/L). All patients underwent induction chemotherapy consisting of daunorubicin (60 mg/m2/d x 3 days) and continuous infusion cytarabine (100 or 200 mg/m2/d x 7 days, for ages <60y and ≥60y, respectively). Patients in CR then received 3 cycles of consolidation chemotherapy which included high dose cytarabine (3 or 1.5 g/m2 on days 1, 3 and 5, for ages <60y and ≥60y, respectively) with daunorubicin 45 mg/m2 on days 1 and 3 added during cycle 1. Results: Ninety percent of patients achieved morphological complete remission (CR) post induction, but 33.3% of these remained molecularly positive by quantitative reverse transcriptase polymerase chain reaction (qR-PCR). The majority of patients (93.6%) subsequently achieved molecular negativity by qR-PCR after the 3rd consolidation cycle. With a median follow-up of 5 years, the estimated 5-year relapse free survival (RFS) was 58% and 5-year overall survival (OS) was 66%. This is in keeping with the earlier AMLSG and UK MRC studies. Only 21% of patients relapsed and the median time to relapse was 10 months. Of the 16 patients who relapsed, 7 underwent allogeneic hematopoietic cell transplantation (HCT) from HLA- matched sibling or unrelated donors, and of these, 4 remain alive and in remission with a median follow up of 8 years. While relapse occurred in 2 of the 4 patients who did not achieve a molecular CR after 3 cycles of consolidation, 13 of 16 relapsing patients had been in a molecular CR after final consolidation and one patient was not evaluated. Therefore, molecular remission post consolidation does not guarantee long term disease free survival. Further molecular analyses and the roles of additional mutations in predicting relapse will be presented. Conclusion: Sustained remissions can be achieved in patients with CBF AML after 3 cycles of high dose cytarabine consolidation, but post consolidation molecular remission does not necessarily preclude relapse. Comprehensive molecular profiling may be better in predicting relapse risk in this group of patients. Table1: Patient characteristics & response N=80 Sex 45 M : 35 F Median age, years (range) 48 (20-80) WBC at diagnosis (x106 cells/L) (range) 13 (1-426) Cytogenetics t(8;21) inv16/t(16;16) 46 (58%) 34 (42%) Response post-induction chemotherapy CR Primary refractory 72 (90%) 8 (10%) Number of consolidation cycles (range) 3 (2-4) Molecular CR post –induction Yes No Not evaluated 16 (20%) 32 (40%) 32 (40%) Molecular CR post –consolidation –cycle 3 Yes No Not evaluated 59 (74%) 4 (5%) 17 (21%) Relapse Yes No Unknown 16 (20%) 59 (74%) 5 (6%) Median time to relapse, months (range) 10 (6-17) Median time to follow up, y (range) 5 (0.5-11.5) Figure 1 : Overall and Relapse free survival in CBF-AML patients. Figure 1 :. Overall and Relapse free survival in CBF-AML patients. Disclosures Gupta: Novartis: Consultancy, Honoraria, Research Funding; Incyte Corporation: Consultancy, Research Funding.
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 | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 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) | 0,001 | 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 ».