B-cell acute lymphoblastic leukemia(B-ALL)is one of the most common pediatric malignancies,characterized by highly heterogeneous genetic alterations.The precise identification of high-risk genetic abnormalities,such as BCR-ABL1,KMT2A rearrangement,and TCF3-HLF,plays a crucial role in risk stratification,the formulation of chemotherapy regimens,and the selection of individualized therapies.High-risk cytogenetics can profoundly impact the trajectory of disease progression and therapeutic outcomes.Regarding therapy,the refinement of treatment strategies through precise molecular classification and risk stratification has catalyzed a gradual paradigm shift in clinical practice.This transition moves away from the traditional reliance on conventional chemotherapy agents toward individualized pharmacotherapy and disease management strategies based on prognostic risk stratification.In recent years,immunotherapy has achieved significant progress in leukemia treatment.Chimeric antigen receptor T-cell(CAR-T)therapy and monoclonal antibodies have emerged as novel therapies for patients with relapsed/refractory(R/R)B-ALL harboring high-risk cytogenetic features.These innovations have significantly improved the prognosis for this patient population.Currently,new clinical trials are continuously advancing.Emerging targeted therapies and cell therapies represented by CAR-T cells have become hot spots of current research and have demonstrated remarkable development potential.This review synthesizes recent therapeutic advances across pediatric B-cell acute lymphoblastic leukemia subtypes harboring high-risk genetic abnormalities,with a focused emphasis on the evolving role of immunotherapy.By critically integrating current evidence,we aim to outline rational strategies for developing safer and more effective therapies that can meaningfully improve clinical outcomes in these high-risk children and adolescents.

B-cell acute lymphoblastic leukemia(B-ALL)is one of the most common pediatric malignancies,characterized by highly heterogeneous genetic alterations.The precise identification of high-risk genetic abnormalities,such as BCR-ABL1,KMT2A rearrangement,and TCF3-HLF,plays a crucial role in risk stratification,the formulation of chemotherapy regimens,and the selection of individualized therapies.High-risk cytogenetics can profoundly impact the trajectory of disease progression and therapeutic outcomes.Regarding therapy,the refinement of treatment strategies through precise molecular classification and risk stratification has catalyzed a gradual paradigm shift in clinical practice.This transition moves away from the traditional reliance on conventional chemotherapy agents toward individualized pharmacotherapy and disease management strategies based on prognostic risk stratification.In recent years,immunotherapy has achieved significant progress in leukemia treatment.Chimeric antigen receptor T-cell(CAR-T)therapy and monoclonal antibodies have emerged as novel therapies for patients with relapsed/refractory(R/R)B-ALL harboring high-risk cytogenetic features.These innovations have significantly improved the prognosis for this patient population.Currently,new clinical trials are continuously advancing.Emerging targeted therapies and cell therapies represented by CAR-T cells have become hot spots of current research and have demonstrated remarkable development potential.This review synthesizes recent therapeutic advances across pediatric B-cell acute lymphoblastic leukemia subtypes harboring high-risk genetic abnormalities,with a focused emphasis on the evolving role of immunotherapy.By critically integrating current evidence,we aim to outline rational strategies for developing safer and more effective therapies that can meaningfully improve clinical outcomes in these high-risk children and adolescents.