The Autoantibody Response to ALK In Pediatric Anaplastic Large Cell Lymphoma: A Children's Oncology Group Report
Notice bibliographique
Résumé
Abstract Abstract 4130 Introduction: Pediatric anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphomas (ALCL) are characterized by the expression of aberrant ALK fusion proteins, the most common of which is nucleophosmin (NPM)/ALK. Interestingly, an autoantibody response to the ALK oncoprotein has been described. Objective: To determine the prevalence and prognostic significance of immune response to the ALK oncoprotein, we analyzed the serum autoantibody response to ALK in a large cohort of uniformly treated advanced stage ALK-positive pediatric ALCL patients enrolled into the ANHL0131 trial (a randomized phase III trial with standard APO versus consolidation with a regimen including vinblastine (J Clin Oncol 28:15s, 2010) and correlated the results with clinical features and patient outcome. Methods: A total of 129 eligible patients were enrolled in this study. Analysis was performed through May 2009 with a median follow-up of 2.9 yrs (0.13-4.7 yrs). ALK expression was determined by immunohistochemistry performed on tissue sections. Patients were stratified according to stage and the involvement of mediastinum, visceral organs, central nervous system and bone marrow. Serum samples were obtained from 64 patients at the time of diagnosis. A subset of the patients (n=43) were also evaluated at the end of induction. An indirect immunoperoxidase technique using cytocentrifuge preparations of COS cells transfected with cDNA encoding NPM/ALK were stained with the patient's serum and the highest dilution of the serum samples at which staining of the transfectants was observed was determined as the titer of the antibody. Three groups of patients were identified: antibody dilutions 0-≤1/750 (low), 1/2025-<1/60750 (intermediate), and ≥1/60750 (high). Results: Autoantibodies to ALK were detected in the serum of 64/64 (100%) patients at the time of diagnosis. Sixteen patients (25%) showed high antibody titers against ALK, 25 patients (40%) intermediate titers and 23 patients (36%) low titers. There was an inverse relationship between autoantibody titers and event-free survival which did not reach statistical significance (p=0.14) due to small number of overall rate of failure (9/64 patients). Patients with high autoantibody titers at diagnosis had a somewhat better 4-year event-free survival (100%) than those with lower antibody titers (intermediate: 82% and low: 75%). Stage 4 and mediastinal disease appeared to be associated with low autoantibody titers (p=0.05). Those 43 patients who were also evaluated at end of induction demonstrated either no change or reduction in autoantibody titers. Conclusions: These results indicate that the autoantibody response to ALK is highly prevalent in patients with ALK-positive ALCLs. They also indicate that the presence of an immune response to the tumor may be associated with clinical response. These results are similar to those reported by NHL-BFM Study (Blood 2010:115:3314-3319). The predictive/prognostic value of autoantibody titer with regard to tumor dissemination and risk of relapse remains to be determined for this treatment regimen. 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 | 0,000 | 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 | 0,001 |
| 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 ».