Pediatric acute lymphoblastic leukemia in the era of blinatumomab: from risk-adapted chemotherapy only to immunotherapy, including concepts of care

Summary Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and one of the major success stories of modern medicine. Cure rates now approach 90–95%, largely because of multinational risk-adapted intensive protocols, optimized central nervous system prophylaxis, improved supportive care, and genetics- and minimal residual disease (MRD)-guided treatment stratification. Nevertheless, relapse remains the leading cause of death, and the current acute and long-term burden of intensive polychemotherapy is substantial. Blinatumomab, a CD19/CD3 bispecific T‑cell engager, has significantly altered the therapeutic landscape of pediatric B‑cell precursor ALL (B-ALL). In relapsed or refractory B‑ALL and in selected frontline settings, randomized studies have shown that blinatumomab can improve clinically meaningful outcome measures and reduce acute-term toxicity when incorporated into chemotherapy backbones. Other applications, including its add-on in infant KMT2A -rearranged B‑ALL and chemotherapy-substitution strategies in newly diagnosed high-risk disease, are highly promising but require careful interpretation due to as-yet small numbers, trial designs, and a lack of mature outcome data. This review integrates the classic principles of pediatric ALL presentation, diagnosis, and treatment with the currently accumulating evidence on blinatumomab, emphasizing both its practice-changing potential and the unresolved questions of MRD surrogacy, resistance, long-term toxicity, cost, and global implementation.