摘要
B系急性淋巴细胞白血病(B-cell acute lymphoblastic leukemia,B-ALL)是儿童最常见的恶性肿瘤之一,其特点是具有高度异质性的遗传学改变。对BCR-ABL1、KMT2A重排、TCF3-HLF等高危遗传学异常的精准识别,在疾病的风险分层、化学治疗(化疗)方案的制定以及个体化用药的抉择等方面发挥着关键作用。高危遗传学异常显著影响疾病的进展态势与治疗转归。从治疗视角来看,通过精细的分子分类和风险分层,治疗策略得以优化,促使临床治疗实践从既往单纯依赖传统化疗药物,逐步转变为依据预后风险分层实施个体化用药及疾病管理模式。近年来,免疫治疗在白血病中取得了显著进展,嵌合抗原受体T细胞(chimeric antigen receptor T-cell,CAR-T细胞)、单克隆抗体等为复发/难治(relapsed/refractory,R/R)的高风险B-ALL患儿提供了新的治疗选择,大幅改善了预后。当前,新的临床试验正持续推进,新兴的靶向治疗以及以CAR-T细胞为代表的细胞免疫治疗是当下的研究热点,展现出巨大的发展潜力。该文综述了儿童伴高风险遗传学异常的各亚型B-ALL在治疗方面的研究进展,并重点讨论目前免疫疗法在其中的应用潜能,以期为制定更有效、更安全的治疗方案从而改善疾病预后提供线索和思路。
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.
作者
唐珺倩
李本尚
TANG Junqian;LI Benshang(Department of Hematology/Oncology,Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 201315,China)
出处
《上海交通大学学报(医学版)》
北大核心
2025年第10期1390-1399,共10页
Journal of Shanghai Jiao tong University:Medical Science
