文章：

婴儿急性淋巴细胞白血病临床试验进展

The evolution of clinical trials for infant acute lymphoblastic leukemia

原文发布日期：2014-04-11

DOI: 10.1038/bcj.2014.17

类型: Review

开放获取: 是

英文摘要：

Acute lymphoblastic leukemia (ALL) in infants has a significantly inferior outcome in comparison with older children. Despite initial improvements in survival of infants with ALL since establishment of the first pediatric cooperative group ALL trials, the poor outcome has plateaued in recent years. Historically, infants were treated on risk-adapted childhood ALL protocols. These studies were pivotal in identifying the need for infant-specific protocols, delineating prognostic categories and the requirement for a more unified approach between study groups to overcome limitations in accrual because of low incidence. This subsequently led to the development of collaborative infant-specific studies. Landmark outcomes have included the elimination of cranial radiotherapy following the discovery of intrathecal and high-dose systemic therapy as a superior and effective treatment strategy for central nervous system disease prophylaxis, with improved neurodevelopmental outcome. Universal prospective identification of independent adverse prognostic factors, including presence of a mixed lineage leukemia rearrangement and young age, has established the basis for risk stratification within current trials. The infant-specific trials have defined limits to which conventional chemotherapeutic agents can be intensified to optimize the balance between treatment efficacy and toxicity. Despite variations in therapeutic intensity, there has been no recent improvement in survival due to the equilibrium between relapse and toxicity. Ultimately, to improve the outcome for infants with ALL, key areas still to be addressed include identification and adaptation of novel prognostic markers and innovative therapies, establishing the role of hematopoietic stem cell transplantation in first complete remission, treatment strategies for relapsed/refractory disease and monitoring and timely intervention of late effects in survivors. This would be best achieved through a single unified international trial.

摘要翻译： 

与年长儿童相比，婴儿急性淋巴细胞白血病（ALL）的预后明显较差。尽管自首个儿科协作组ALL试验开展以来，婴儿ALL的生存率初期有所提高，但近年来的不良结局已呈现平台期。历史上，婴儿一直按照风险适应性儿童ALL方案进行治疗。这些研究对于明确制定婴儿特异性方案的必要性、界定预后分类以及各研究组之间需要采取更统一方法以克服低发病率导致的入组限制具有关键意义，进而推动了协作性婴儿特异性研究的开展。里程碑式的成果包括：在发现鞘内及大剂量全身治疗作为中枢神经系统疾病预防的优越有效策略后，颅脑放疗被淘汰，同时神经发育结局得到改善。对独立不良预后因素（包括混合谱系白血病基因重排的存在和低龄）的全面前瞻性识别，为当前试验中的风险分层奠定了基础。婴儿特异性试验已明确了传统化疗药物强化的限度，以优化疗效与毒性间的平衡。尽管治疗强度存在差异，但由于复发与毒性之间的平衡，近期生存率并未得到改善。最终，为改善婴儿ALL的预后，仍需解决的关键领域包括：新型预后标志物的识别与调整、创新疗法的应用、明确造血干细胞移植在首次完全缓解中的作用、制定复发/难治性疾病的治疗策略，以及对幸存者晚期效应进行监测和及时干预。这些目标最好通过一项统一的国际试验来实现。

原文链接：

The evolution of clinical trials for infant acute lymphoblastic leukemia