Prognostic Factors and Survival Outcomes in Pediatric Acute Lymphoblastic Leukemia: A Real-World Retrospective Cohort Study from a Tertiary Care Center in North India.

Background Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with outcomes varying significantly across different populations. While survival rates have significantly improved in high-income countries, data from low- and middle-income countries (LMICs) remain heterogeneous. The Kashmir region in India represents a unique population with distinct genetic and demographic characteristics, including high rates of consanguinity and potential pharmacogenomic variability. This study aimed to evaluate the prognostic significance of clinical and biological factors and their impact on survival outcomes in pediatric ALL patients treated in a real-world tertiary care setting. Methods This retrospective cohort study included pediatric patients (aged 1-18 years) diagnosed with ALL between June 2016 and November 2023 at the State Cancer Institute, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu & Kashmir, India. All patients were treated according to the Berlin-Frankfurt-Münster (BFM)-95 pediatric ALL protocol with risk stratification based on clinical parameters, cytogenetics, and early treatment response. Key prognostic variables included age, gender, leukocyte count at presentation, immunophenotype, cytogenetics, Day 8 prednisolone response, and Day 33 bone marrow and minimal residual disease (MRD) status post induction. Survival outcomes were assessed using Kaplan-Meier analysis, and prognostic factors were evaluated using univariate and multivariate Cox regression models. Results A total of 232 patients were analyzed after exclusions. The median age was 8.5 years, with a male predominance (58.2%, n=135). B-cell ALL constituted (84.9%, n=197) of cases. A good prednisolone response on Day 8 was observed in 96.6% (n=224) of patients. On day 33, 89.7% (n=208) achieved bone marrow remission and 82.8% (n=192) attained MRD negativity. After a median follow-up of 49 months, 43 patients (18.5%) relapsed, and 56 patients (24.1%) died. The estimated five-year overall survival (OS) and event-free survival (EFS) were 74.5% and 66.9%, respectively. On univariate analysis, favorable prognostic factors included younger age, B-cell phenotype, absence of high-risk cytogenetics, MRD negativity, and marrow remission at Day 33. On multivariate analysis, MLL (mixed lineage leukemia) gene rearrangement, MRD positivity, lack of marrow remission at Day 33, and CNS involvement were independent predictors of inferior survival. Conclusion This study demonstrates that outcomes of pediatric ALL in Kashmir are comparable to those in other resource-limited settings and confirms the pivotal role of early treatment response, particularly MRD status, in prognostication. Despite unique genetic and demographic factors, BFM-based risk-adapted therapy remains effective in this population. These findings underscore the need for enhanced access to molecular diagnostics and MRD assessment to further optimize outcomes and enable personalized therapy in this region.