CELL INTELLIGENCE · 肿瘤细胞治疗研究

Acute leukemia remains a life-threatening hematologic malignancy with historically poor outcomes in relapsed/refractory and elderly patients. Over the past decade, measurable residual disease (MRD) has evolved from a prognostic indicator to a core determinant of risk stratification and clinical decision-making, driving a paradigm shift toward precision medicine. Technological innovations-including leukemia stem cell (LSC)-directed MRD detection, single-cell sequencing, and personalized digital polymerase chain reaction (PCR)-have markedly improved the sensitivity and specificity of MRD monitoring, enabling the early identification of patients at ultrahigh risk of relapse. Concurrently, targeted therapy has moved from salvage to frontline standard care; the use of FLT3, IDH1/2, and BCR-ABL1 inhibitors combined with chemotherapy or immunotherapy has significantly prolonged remission, improved MRD negativity rates, and redefined prognostic stratification. Novel cellular therapies, particularly CD19/CD22-targeted chimeric antigen receptor T (CAR-T) and bispecific T-cell engagers, have revolutionized the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia, and allogeneic hematopoietic stem cell transplantation (allo-HSCT), optimized by the "Beijing Protocol" for haploidentical donors, remains the cornerstone of curative intent. Low-toxicity regimens, such as venetoclax plus hypomethylating agents, have transformed care for elderly or unfit patients, shifting goals from palliation to long-term survival. Despite these advances, challenges, including antigen escape, CAR-T-cell persistence, graft-versus-host disease, and treatment accessibility, persist. This commentary summarizes landmark progress in MRD-guided precision stratification, targeted therapy, cellular immunotherapy, and allo-HSCT; discusses unresolved clinical bottlenecks; and proposes future directions centered on dynamic MRD monitoring, personalized targeted-immunotherapy combinations, and risk-adapted transplantation strategies to further improve cure rates and long-term survival across all acute leukemia subtypes.