Additional Induction Intrathecal Cytarabine for Patients with CNS2 Disease at Diagnosis Is Not Beneficial for Patients with B-ALL Treated on Children's Oncology Group Protocols AALL0932 and AALL1131
Notice bibliographique
Résumé
Background: Children's Oncology Group (COG) trials AALL0932 and AALL1131 enrolled children with newly diagnosed National Cancer Institute (NCI) standard-risk (SR) and high-risk (HR) B-ALL from 2010-2019 and 2012-2019, respectively. In 2016, COG amended these trials to incorporate additional induction intrathecal (IT) therapy for patients with B-ALL and CNS2 status [CSF <5/μL WBCs and cytospin positive for blasts; or traumatic lumbar puncture (LP) with ≥5/μL WBCs and cytospin positive for blasts that was negative by Steinherz/Bleyer algorithm]. Based on data demonstrating worse outcomes for CNS2 patients enrolled on prior COG B-ALL trials compared to those without CNS disease at diagnosis (CNS1), COG added IT cytarabine on day 4, maintained day 8 IT methotrexate, then continued twice weekly IT cytarabine until 3 consecutive LPs returned negative cerebrospinal fluid (CSF) results. Methods: Event free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were compared among CNS2 pre- vs post-amendment patients, stratified by NCI risk group. Multivariable models were also constructed to adjust for demographic and disease variables. Results: When stratified by trial, pre- and post-amendment patients did not differ significantly by demographic or disease factors, including age at diagnosis, end of induction bone marrow MRD status, and blast cytogenetics. For patients with NCI SR B-ALL and CNS2 enrolled on AALL0932 (8% of study population, n=535 pre-amendment, n=207 post-amendment), the 5-year EFS pre- vs post-amendment was 86.7% (SE, 1.5%) vs 88.9% (SE, 2.3%), p=0.44, and 5-year OS pre- vs post-amendment was 95.5% (SE, 0.9%) vs 96.0% (SE, 1.5%), p=0.50. The 5-year CIR for isolated CNS relapse was 3.6% (SE, 0.8%) vs 4.0% (SE, 1.4%) pre- vs post-amendment, p=0.71, and for combined marrow and CNS relapses was 1.0% (SE, 0.4%) vs 1.0% (SE, 0.7%), p=0.71. Among post-amendment NCI SR patients (CNS1 n=2033, CNS2 n=207), the adverse impact of CNS2 status remained statistically significant, with 5-year EFS of 93.2% (SE, 0.6%) vs 88.9% (SE, 2.3%) for CNS1 vs CNS2, p=0.025. For patients with NCI HR B-ALL and CNS2 status (16.6% of study population, n=488 pre-amendment, n=313 post-amendment), the 5-year EFS pre- vs post-amendment was 66.5% (SE, 2.4%) vs 73.5% (SE, 3.4%), p=0.095 and OS pre- vs post-amendment was 80.2% (SE, 2.0%) vs 84.0% (SE, 2.8%), p=0.20. The 5-year CIR for isolated CNS relapse was 5.9% (SE, 1.1%) vs 5.6% (SE, 1.4%) pre- vs post-amendment, p=0.92, and for combined marrow and CNS relapses was 2.7% (SE, 0.8%) vs 0.7% (SE, 0.5%) pre- vs post-amendment, p=0.068. The post-amendment impact of CNS status on outcomes remained significant for NCI HR patients (CNS1 n=1326, CNS2 n=313), with 5-year EFS of 78.4% (SE 1.5%) vs 73.5% for CNS1 vs CNS2, p=0.049. In multivariable analyses conducted separately for AALL0932 and AALL1131 and adjusting for disease prognosticators and race/ethnicity, treatment post-amendment was not significantly associated with any difference in EFS (AALL0932: hazard ratio 0.99, 95CI 0.6-1.6, p=0.95; AALL1131: hazard ratio 0.80, 95CI 0.6-1.1, p=0.14). Additional analyses evaluating subgroups defined by cytogenetics (favorable, neutral, unfavorable) or disease response did not find any subpopulation that significantly benefited from extra IT chemotherapy. The additional therapy was not associated with an increase in toxicity. Conclusions: Additional IT cytarabine during induction for patients with CNS2 disease on AALL0932 and AALL1131 did not improve outcomes or mitigate the adverse prognostic impact of CNS2 status. Rates of CNS2 status and impact on outcome vary greatly between cooperative groups, and factors such as variability in CSF analysis and post-induction therapy need to be considered in order to identify this population accurately and treat accordingly. Given these results showing lack of improvements in outcome and concerns surrounding repeated anesthesia exposure, future frontline B-ALL COG studies will not include additional IT cytarabine for the CNS2 population. Alternative methods of improving outcomes for CNS2 patients are needed.
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 | 0,002 | 0,006 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».