Abstract B039: Investigations on ethnographic disparities in molecular epidemiology of pediatric ALL and its impact on clinical outcome as well as cancer management planning strategies
Notice bibliographique
Résumé
Abstract Introduction: Pediatric acute lymphoblastic leukemia (P-ALL) is globally most common pediatric cancer. Cytogenetics remains the independent predictor of its clinical outcomes despite technological and treatment advances in 21st century. Tthe Fusion oncogenes (FOs) caused by chromosomal abnormalities not only play a significant role in the development of pediatric B cell acute lymphoblastic leukemia (ALL) but also serve as basis of its prognostic stratification (favorable prognosis versus poor prognosis) as well as clinical protocol selection (3-drug protol for favorable prognosis group versus 4-5 drug protocol for poor prognostic group). The predominant fusion oncogenes (FOs) include BCR-ABL, MLL-AF4, ETV6-RUNX1, and TCF3-PBX1, all of which carry significant prognosis and treatment selection implications. Furthermore, the frequencies of FOs exhibit ethnic variances. P-ALL is Pakistan have historically poor outcome for which underlying genetic reasons are unexplored at national level. Therefore, we aimed to investigate frequency of FOs of prognostic significance in P-ALL, their treatment outcome and survival.Patients & Methods: Overall,188 clinically diagnosed P-ALL patients (age range: 1-15 years) were recruited from different regional hospitals of Pakistan and FOs studied by employing reverse transcriptase-polymerase chain reaction (RT-PCR) and interphase fluorescence in situ hybridization (FISH). The clinical data data was analyzed using SPSS version 25.Results: FOs were identified in 87.2% of the individuals. The average overall survival was 70.9 weeks, with a 3-year survival rate of 31.9% and a 3-year relapse-free survival rate of 18.1%. Four individuals succumbed to medication toxicities. ETV6-RUNX1 (19.14 %) demonstrated a higher survival rate (110.9 weeks; p = 0.03). TCF3-PBX1 (2.1 %) was linked to a worse outcome and an increased risk of relapse in the central nervous system (CNS). MLL-AF4 (18.1 %) was more prevalent in the 8- to 15-year age group (24/34; p = 0.001) and was associated with organomegaly, low platelet count, and poor survival. BCR-ABL (47.9 %) was associated with older age (7–15 years, 52/90), lower remission rates, shorter survival (43.73 ± 4.24 weeks), and a higher white blood cell count. BCR-ABL results were confirmed using interphase FISH. MLL-AF4 and BCR-ABL were found in 66% of B-ALL cases, which typically occurred in older children. Discussion, conclusions &recommendations: This study reveals that the occurrence of BCR-ABL FO in pediatric ALL within a specific ethnic group is the highest ever reported. These findings align with earlier studies conducted in our region. Two-thirds of pediatric B-ALL cases in South-East Asia have been shown to have a bad prognosis due to the presence of BCR-ABL and MLL-AF4. This is likely the cause of the previously reported low survival rates for childhood ALL in this region. Additionally, the integration of tyrosine kinase inhibitors and hematopoietic stem cell transplantation facilities should be implemented to enhance treatment outcomes for patients in developing nations. Citation Format: Sarah Al-Mukhaylid, Prof Dr Zafar Iqbal, Nawaf Alanazi, Tashfin Awan. Investigations on ethnographic disparities in molecular epidemiology of pediatric ALL and its impact on clinical outcome as well as cancer management planning strategies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B039.
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 | 0,002 |
| 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 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 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 ».