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
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".