Acute lymphoblastic leukemia (ALL) is the most common disease in pediatric oncology. The history of developmental therapeutics for ALL began in the 1960s with the repetition of “unreliable” medical interventions against this lethal disease. By the 1990s, the development of multi-agent chemotherapy and various types of supportive care rendered ALL treatable. Highly sophisticated, molecular, diagnostic techniques have enabled highly accurate prediction of the relapse risk, and the application of risk-adapted treatments has increased the survival rate in the standard-risk group to nearly 100% in most European nations and North America. Incorporation of state-of-the-art, molecularly targeted agents and novel treatments, including cell and immunotherapy, is further improving outcomes even in the high-risk group. On the other hand, the financial burden of treating children with ALL has increased, imperiling the availability of these diagnostic and treatment strategies to patients in low- and middle-income countries (LMICs). The fundamental treatment strategy, consisting of corticosteroid and classical cytotoxic therapy, has achieved fairly good outcomes and should be feasible in LMICs as well. The present review will discuss the history of developmental therapeutics for childhood ALL in various countries through an extensive literature review with the aim of proposing a model for a treatment backbone for pediatric ALL. The discussion will hopefully benefit LMICs and be useful as a base for future clinical trials of novel treatments.
急性淋巴细胞白血病（ALL）是儿童肿瘤学中最常见的疾病。ALL发展性治疗的历史始于20世纪60年代，当时针对这种致命疾病重复使用“不可靠”的医疗干预措施。到20世纪90年代，多药联合化疗及各类支持治疗的发展使ALL成为可治之症。高度精密的分子诊断技术能够实现复发风险的高精度预测，而风险适应治疗的应用使得大多数欧洲国家和北美地区标准风险组的生存率提升至近100%。即使在高危组中，引入先进的分子靶向药物及包括细胞与免疫疗法在内的新型治疗手段，也进一步改善了治疗效果。然而，儿童ALL治疗的经济负担日益加重，威胁到中低收入国家（LMICs）患者获取这些诊断和治疗策略的可能性。以皮质类固醇和经典细胞毒疗法为基础的核心治疗策略已取得相当良好的疗效，在LMICs也应具备可行性。本综述将通过广泛的文献回顾，探讨各国儿童ALL发展性治疗的历史，旨在提出儿童ALL治疗主干方案的模式。相关讨论有望惠及LMICs，并为未来新型治疗的临床试验提供基础参考。
Treatment of Pediatric Acute Lymphoblastic Leukemia: A Historical Perspective
肿瘤(癌症)患者之家