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Acute lymphocytic leukemia (ALL) is a commonly diagnosed cancer in children. Despite technological advancements to improve treatment and survival rates, there has been a steady increase in the incidence of ALL and treatment failures. This paper discusses the pathogenic interaction between genetic and environmental factors leading to childhood ALL. It evaluates the current treatment guidelines and notable obstacles leading to resistance, relapse, and treatment toxicities. The review evaluates a 10-year trend in the management guidelines of pediatric ALL through a systematic literature review of records from 2012 to 2023. Findings show that improvement in the five-year survival rates, notwithstanding rates of relapse and incurable diseases, is still high. Furthermore, several risk factors, including an interplay between genetic and environmental factors, are largely contributory to the outcome of ALL treatments and its overall incidence. Moreover, huge financial costs have remained a significant challenge in outcomes. There remains a need to provide individualized treatment plans, shared decision-making, and goals of care as parts of the management guidelines for the best possible outcomes. We expect that future advancements will increase overall survival rates and disease-free years., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ekpa et al.)

Competing Interests: The authors declare no competing interests.