What Is the Prognostic Relevance of Responses Less Than a CR(Sub-CR) to Initial AML Treatment?
Notice bibliographique
Résumé
Context: Achievement of CR has long been one of the goals of AML treatment. Over the years, less stringent criteria for defining CR (sub-CR) have been developed to incorporate patients in clinical trials and to facilitate regulatory approvals. In both the intensive and non-intensive up-front treatment scenarios, sub-CR responses are associated with inferior outcomes compared to those achieving true CR. However, it is not clear whether sub-CR response comprises a prognostic factor independent of the underlying disease biology. Design: Retrospective single center study Patients and methods: 363 AML patients CR or sub-CR response between Jan 2019 to Jan 2023 were included. Sub-CR responses included CRi, CRh, and MLFS per ELN 2022. Univariate and multivariable logistic regression models were conducted to assess the association between clinical variables and CR/sub-CR response. Kaplan-Meier curves were generated for EFS and OS, and differences were tested using the log-rank test. All statistical analyses were performed using the EZR software (a modified version of R commander (version 1.5.4)). Objectives: Primary objective: To identify predictors of sub-CR response. Secondary objectives: To compare EFS and OS between CR and sub-CR patients, in both overall population and AML subgroups Results: Among the 363 patients, 227 patients achieved CR, and 136 sub-CR. Sub-CR responses included CRi/h(75) and MLFS(61). By UVA, sub-CR response was associated with secondary AML(OR: 2.801(95%CI[1.70 - 4.63]); p<0.0001), adverse cytogenetics(OR: 5.008[1.36 - 18.35]; p 0.02), intermediate cytogenetics(OR: 6.5[1.92 - 22.03]; p 0.02), ELN adverse risk(OR: 5.95[3.2 - 11.1]; p<0.001), ELN intermediate risk(OR: 2.11[1.07 - 4.15]; p<0.0001), unmutated NPM1 (OR: 1.96[1.23 - 3.13]; p 0.02), MDS-related mutations(OR: 4.49[2.84 - 7.09]; p<0.0001) and non-intensive treatment (OR: 8.612[4.98 - 14.87]; p<0.001). On MVA, sub-CR responses were associated with non-intensive treatment (OR: 6.273 [3.46 - 11.35]; p<0.0001), ELN adverse risk (OR: 3.033 [1.49 - 6.18]; p 0.0073) and MDS-related mutations (OR: 2.757[1.57 - 4.83]; p 0.0004). The 24 month-EFS was inferior(p<0.0001) in patients with sub-CR (33.5% [25.2 - 41.7]) compared those with a CR (58.1% [51.1 - 64.5]). Similarly, 24-month OS was inferior in the sub-CR group (45.3% [36.3 - 53.9] (sub-CR) vs 67.5% [60.6 - 73.5] (CR); p<0.0001). This difference persisted after censoring for transplant (HSCT) (26.4% [17.6 - 36.1] (sub-CR) vs 54.6% [45.9 - 62.6] (CR); p<0.0001). The inferior OS of the sub-CR group was seen in ELN favorable (24-month OS: 56.2%(sub-CR) vs 84.3%(CR); p 0.008) and intermediate risk (24-month OS: 52.9%(sub-CR) vs 64.9%(CR); p-0.02), but not in adverse risk (24-month OS: 39.8%(sub-CR) vs 52.3%(CR); p-0.187). Inferior OS of sub-CR was observed in intensively treated patients (24-month OS:52.7%(sub-CR) vs 71.7%(CR); p-<0.0001), but not in non-intensively treated patients (24- month OS: 37.6%(sub-CR) vs 22.5%(CR); p-0.149). When MRD status was considered, we did not observe a significant difference in the 24-month OS between sub-CR and CR, whether MRD negative (24-month OS: 56.6%(sub-CR) vs 67.7%(CR); p-0.06) or positive (24-month OS: 40.3%(sub-CR) vs 62.95(CR); p-0.08). In patients who underwent HSCT, there was no significant difference in the 24-month OS between sub-CR and CR (64%(sub-CR) vs 72.4%(CR); p-0.0504) whereas a difference was noted in the non-transplanted population (31.6%(sub-CR) vs 62.5%(CR); p-<0.0001). Conclusions: We conclude that sub-CR responses in AML reflect both underlying disease biology and type of treatment administered. Sub-CR responses were more common in patients with adverse pre-treatment characteristics (ELN adverse risk and MDS-related mutations), and in non-intensively treated patients. In these subgroups, a sub-CR response did not confer inferior survival. In contrast, sub-CR response was associated with inferior survival in intensively treated patients and in favorable/intermediate risk AML. The OS effects of sub-CR response were MRD independent in our hands, and HSCT appeared to be able to overcome the negative OS impact of sub-CR status.
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 | 0,013 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».