Excess Treatment-Related Mortality in Obese Children and Adolescents with Acute Myeloid Leukemia on AAML0531: A Report from the Children's Oncology Group
Notice bibliographique
Résumé
Abstract Background: Therapy for children with acute myeloid leukemia (AML) is intensive and treatment-related mortality (TRM) occurs in about 5 to 10% of patients. Previous data illustrated that obese children and adolescents with AML treated according to CCG 2961 were more likely to experience TRM, with HR 2.66 (95% CI 1.38-5.11; P = 0.003), when compared to middleweight patients. Since this trial, the backbone of AML chemotherapy and supportive care have changed and thus, it is unknown whether the impact of obesity persists in contemporary trials. The objective was to determine whether obesity was associated with increased TRM, reduced survival and prolonged compared to middleweight patients with AML. Methods: AAML0531 enrolled patients between August 14, 2006 and June 15, 2010. For this analysis, we included patients 0 to 18 years of age with de novo AML. Chemotherapy consisted of 5 cycles of chemotherapy and patients were randomized to receive or not receive gemtuzumab once during Induction I and Intensification II. Best allogeneic donor hematopoietic stem cell transplantation (HSCT) was recommended for those with > 15% bone marrow blasts after Induction I in those without favorable risk cytogenetics and poor risk cytogenetics irrespective of response following Induction I. Matched family donor HSCT was recommended for those with good response after Induction I with standard risk cytogenetics and an available donor. Obesity was defined using definitions from the Centers for Disease Control and Prevention (CDC). Underweight was defined as a body mass index percentile less than 5th percentile, and obese 95th percentile and greater. Categories were determined using z-scores for the weight-for-height data for those 0 to 2 years of age. All outcomes were censored at the time of HSCT. The primary outcome was TRM, defined as death as first event occurring on therapy or within 30 days of going off therapy. Cumulative incidence of TRM was estimated treating relapse and failure as competing events. Kaplan Meier analysis was conducted for overall survival (OS), event free survival (EFS), and disease free survival (DFS). Cumulative incidence of relapse rate (RR) was estimating treating deaths as competing events. Results: There were 1004 patients included. When comparing middleweight and obese patients, there was no significant difference in gender (P=0.814), white vs non-white race (P=0.116), cytogenetic risk group (all P>0.05) or MRD positivity after Induction 1 (P=0.750). The median age was higher for obese patients (12.0 vs 9.4 years; P=0.007 years) compared with middle weight patients. The proportion of patients who were Hispanic or Latino patients was higher among obese compared with middle weight patients (28% vs 17%; P=.001). Survival outcomes are shown in Table 1. When evaluating median time to neutrophil recovery, obese patients, when compared to middleweight patients, had shorter duration of neutropenia for cycles 1-3 (P<0.05). Conclusions: TRM rates continue to be higher for obese patients treated with contemporary AML protocols. Toxicity is not mediated through prolonged neutropenia. Future work should compare the rate of toxicity among obese versus non-obese patients and evaluate the impact of underweight status. Disclosures No relevant conflicts of interest to declare.
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 | 0,001 |
| 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 | 0,000 | 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 ».