BETWEEN CURE AND CHALLENGE: THE ROLE OF CAR-T THERAPY IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

Abstract

Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in childhood and, despite major therapeutic advances, relapse and refractoriness remain leading causes of mortality. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as one of the most transformative innovations in modern medicine, offering unprecedented responses in children lacking effective options. Pivotal trials such as ELIANA demonstrated complete remission rates above 80% and overall survival exceeding 70% at one year, findings confirmed in real-world settings. However, the durability of these responses is inconsistent, with relapse in up to 40% of cases, frequently associated with antigen escape and limited CAR-T persistence. Severe immune-mediated toxicities, notably cytokine release syndrome and neurotoxicity, pose additional clinical and ethical challenges in pediatrics. Recent advances, including dual-target CAR-T, allogeneic “off-the-shelf” platforms, and combinations with other immunotherapies aim to expand efficacy and reduce risks, though long-term validation is still lacking. Meanwhile, prohibitive costs and specialized infrastructure requirements restrict access in low- and middle-income countries, underscoring the tension between scientific innovation and global health inequities. CAR-T therapy should thus be regarded not only as a therapeutic breakthrough but as a landmark that reveals the limits of translating innovation into equity. Its true impact will be measured by its ability to evolve into a safer, more durable, and accessible intervention capable of transforming pediatric ALL care worldwide.