Cell-based Therapies in Acute Lymphoblastic Leukemia Treatment: Current Advancements and Limitations

Abstract

Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by clonal expansion of immature lymphoid precursors in the bone marrow and extramedullary sites. Although frontline chemotherapy induces remission in most patients, relapse, treatment resistance, and cumulative toxicities remain major challenges. Targeted therapies, including antibody-based agents and tyrosine kinase inhibitors, improve outcomes in selected patients but are limited by cost, durability, and accessibility. Consequently, cell-based interventions, particularly hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor (CAR)-based immunotherapies, have emerged as critical strategies for relapsed or refractory ALL. Although CD19-directed CAR-T cell therapy demonstrates remarkable potential to induce durable remissions, cytokine release syndrome, neurotoxicity, antigen escape, high manufacturing costs, and limited scalability remain significant challenges. Emerging CAR-based approaches, including CAR-NK and other engineered immune cells, along with dendritic cell-based vaccines, represent complementary strategies to enhance safety and efficacy. This review highlights current cell-based therapies for ALL and approaches to improve safety, persistence, and clinical outcomes.