Abstract 4162: The importance of age-related cytokines in chronic lymphocytic leukemia
Notice bibliographique
Résumé
Abstract Chronic lymphocytic leukemia (CLL) is a disease of the elderly with the median age at diagnosis being 72 years. Prognosis is highly variable with the relative survival progressively worsening after age 65 years. In this study we have evaluated whether the age-related cytokines, IL-6, IL-8 and TNF-alpha, play a role in the poor survival of elderly patients with CLL. The plasma levels and biological effects of the age-related cytokines, IL-6, IL-8 and TNF-alpha, were evaluated in 193 CLL patients of varying ages. Patients were chosen randomly to reflect the age spectrum and sex distribution of the Manitoban CLL population. As predicted from population studies, the survival of patients progressively worsened with age, with the primary causes of death being CLL or one of its complications (infection or second tumors). Cytokine levels were increased in CLL compared to 37 age- and sex-matched controls. A third of patients aged </=65 years had increased IL-6, compared to 10% in patients < 65. A high correlation was found between the plasma levels of these three cytokines with age and Beta2-microglobulin (a measure of tumor burden). The plasma levels of the cytokines also correlated with each other, suggesting they increased in parallel. In contrast, the standard CLL prognostic markers IgVH mutational status, ZAP-70, CD38 and Rai stage did not correlate with cytokine levels or age. Patients with increased IL-6 or IL-8 had a poorer survival than those with normal levels. For IL-6, this difference was more marked for those </=65 years. Furthermore, focusing on older patients, multivariate analysis with backward selection of variables showed IL-6 and Beta2-microlgobulin to be significant predictors of survival, while the mutational status and Rai stage were not significant. The cause of death was due to CLL-related causes and not to frailty or cardiovascular disease. However, increased cytokine levels correlated with a higher lifetime incidence of cardiovascular disease. Thus, one source of cytokines may be cardiovascular disease, although CLL cells also secreted low amounts of IL-6 and IL-8. The two cytokines, in turn, significantly increased the adhesion of leukemic cells to stromal cells, suggesting that these cytokines may influence the microenvironment, which would contribute to poor survival. In summary, IL-6 and IL-8 are predictors of survival in CLL, where IL-6 is a stronger predictor of survival in older patients than mutational status or Rai stage. Importance of IL-6 and IL-8 may be associated with their role in facilitating the leukemic-stromal cell interaction. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4162. doi:10.1158/1538-7445.AM2011-4162
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 | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| 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 ».