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儿童 ALL 治疗的演变:从氨基蝶呤到 CAR-T 细胞疗法:全球进展、印度适应性调整及对中低收入国家的启示

英文原题:Evolution of Therapy in Pediatric ALL From Aminopterin to Chimeric Antigen Receptor T-Cell Therapy: Global Advances, Indian Adaptations, and Lessons for Low- and Middle-Income Countries.

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Evolution of Therapy in Pediatric ALL From Aminopterin to Chimeric Antigen Receptor T-Cell Therapy: Global Advances, Indian Adaptations, and Lessons for Low- and Middle-Income Countries.

PubMed 2026/03/17(内容时间) JCO Glob Oncol Q2 · IF 3.8(JCR 2025)

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研究思路按摘要原文分段

低收入和中等收入国家(LMICs)儿童ALL的生存结局已显示出逐步改善,紧随高收入国家取得的显著成果,尽管存在一定的时间滞后。这是自20世纪40年代以来数十年努力的结果。

我们对1948年至2025年儿童ALL演变过程中的既往文献、治疗创新和里程碑式试验进行了叙述性综述,并类比了这些内容在印度背景下是如何被采用的。该综述对关键治疗原则和随时间变化的生存趋势进行了历史性总结。

在全球范围内,多药化疗、CNS导向治疗、风险分层强化治疗、微小残留病指导治疗和免疫治疗等原则塑造了现代ALL管理的主干。每一步都推动了生存率的稳步提升,从20世纪60年代的4%升至当前的96%。在印度,这些原则通过多中心方案841、国际癌症治疗与研究网络方案以及最终的风险适应性印度儿童白血病协作方案依次被采纳,使生存率从20世纪70年代的近10%提高到近期试验中的61%-76%。然而,由于治疗相关死亡率(12%)、CNS复发以及新药、免疫治疗和先进诊断手段的可及性有限,生存率仍比全球基准低约20%。近来,低强度本地化适应方案和可负担的国产(CD19)CAR-T 细胞疗法有望部分缩小这一差距,尽管治疗毒性和blinatumomab可及性有限仍构成挑战。

印度儿童ALL的诊疗表明,尽管面临诸多挑战,包括经济限制、药物可及性有限、就诊延迟和治疗放弃,但基于证据的方案调整、卫生系统强化和多中心协作可以改善LMICs中的结局。

展开英文摘要原文

Survival outcomes for childhood ALL in low- and middle-income countries (LMICs) have shown gradual improvement, closely following the remarkable outcomes achieved in high-income countries, albeit with some time lag. This has been achieved by decades of efforts since the 1940s.

We conducted a narrative review of the previous literature, therapeutic innovations, and landmark trials in the evolution of childhood ALL from 1948 to 2025 and drew an analogy of how they have been adapted in the Indian context. The review gives a historical summary of the key therapeutic principles and survival trends over time.

Globally, the principles of multiagent chemotherapy, CNS-directed therapy, risk-stratified intensification, minimal residual disease-guided treatment, and immunotherapy have shaped the backbone of modern ALL management. Each step has contributed to the steady rise in survival from 4% in the 1960s to 96% in the current era. In India, these principles were adopted sequentially with multicentre protocol 841, International Network for Cancer Treatment and Research protocols, and finally the risk-adapted Indian Collaborative Childhood Leukaemia protocol, resulting in improved survival from nearly 10% in the 1970s to 61%-76% in recent trials. However, survival remains approximately 20% lower than global benchmarks because of treatment-related mortality (12%), CNS relapses, and limited access to newer drugs, immunotherapy, and advanced diagnostics. Lately, low-intensity locally adapted regimens and affordable indigenous (CD19) chimeric antigen receptor T-cell therapy offer promise to partly narrow the gap although treatment toxicity and limited blinatumomab access remain challenging.

The care of childhood ALL in India demonstrates how evidence-based protocol adaptations, health system strengthening, and multicentric collaboration can improve outcomes in LMICs despite several challenges, including financial constraints, limited drug access, late presentation, and treatment abandonment.

论文信息

作者
Mohapatra D、Meena JP、Gupta AK、Seth R
单位
Division of Pediatric Oncology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.India
文献类型
综述
期刊
JCO global oncology2026 Mar
原文标识
PubMed 41843833 · DOI 10.1200/GO-25-00478