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
Authors: Al-Mukhaylid Sarah , Zafar Iqbal Prof Dr , Alanazi Nawaf , Awan Tashfin 
Published: September 2024

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.