Translational advances in the treatment of childhood acute lymphoblastic leukemia: narrative review of current and emerging molecular and immunotherapies

BACKGROUND AND OBJECTIVE: Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy of lymphoid origin in children. The prognosis for newly diagnosed ALL in the pediatric population is generally favorable, with a 5-year overall survival rate of more than 90%. Though conventional therapy has led to meaningful improvements in cure rates for new-onset pediatric ALL, one-third of patients still experience a relapse or refractory disease, contributing to a significant cause of pediatric cancer-related mortality. METHODS: An extensive literature review was undertaken via various databases of medical literature, focusing on both results of larger clinical trials, but also with evaluation of recent abstract publications at large hematologic conferences. KEY CONTENT AND FINDINGS: Remission is achievable in most of these patients by re-induction with currently available therapies, but the long-term overall survival rate is deemed suboptimal and remains a therapeutic challenge. As part of never-ceasing efforts to improve pediatric ALL outcomes, newer modalities, including targeted molecular therapies as well as immunotherapy, and chimeric antigen receptor (CAR) T-cell therapy, are currently being employed to increase treatment effectiveness as well as lessen the side effects from conventional chemotherapy. These approaches explore the use of early genome-based disease characterization and medications developed against actionable molecular targets. CONCLUSIONS: Additional clinical research is nonetheless required to learn more about the potentially harmful effects of targeted therapies and investigate the possibility of these agents replacing or decreasing the use of conventional chemotherapy in treating pediatric ALL.