The use of Minimal Residual Disease detection to improve treatment outcome in childhood acute lymphoblastic leukaemia

白血病是最常见的儿童癌症，约占所有病例的35%。尽管进行了密集的治疗，但这种疾病经常在骨髓中复发，尽管根据一些标准，儿童在确诊时被分为预后良好组和预后较差组，但两组患者都会复发。我们和其他人获得的证据表明，在预后良好的组中及早发现治疗反应差，并在癌症负担处于较低水平时实施替代治疗，很有可能提高患者的存活率。在这方面，我们最近开发了一种新的分子遗传学技术，可以检测和定量非常低水平的残留白血病，具有极高的敏感性和特异性。这项技术非常适合在常规临床环境中使用，作为这一发展的结果，我们现在已经建立了一项临床试验(ANZCCSG研究VIII)，在该试验中，结果不佳的患者将接受更密集的治疗，以了解这是否会提高存活率。这项试验还将涉及一些研究问题，包括治疗结束时残留白血病的水平是否能够预测未来的复发，否则不会被怀疑。预计这项临床试验将有助于为白血病儿童确定最合适的治疗策略。该项目处于世界此类研究的前沿，对白血病儿童的治疗管理具有重大影响，并有可能直接为改善这种最常见的儿童癌症的存活率做出贡献。

Leukaemia is the most common childhood cancer, representing approximately 35% of all cases. Despite intensive therapy, the disease frequently recurs in the bone marrow and although children are classified into good and poor prognosis groups at diagnosis based on a number of criteria, relapses nevertheless occur in both groups. Evidence obtained by ourselves and others, suggests that early detection of poor treatment response in the otherwise good prognosis group, and the implementation of alternative therapy when the cancer burden is at a low level, has a high likelihood of improving patient survival. In this regard, we have recently developed a novel molecular genetic technique that can detect and quantitate very low levels of residual leukaemia with great sensitivity and specificity. This technique is ideally suited for use in the routine clinical setting, and as a result of this development, we have now established a clinical trial (ANZCCSG Study VIII) in which patients who have a bad result on this test, will be given more intensive treatment to see if this improves survival rates. A number of research questions will also be addressed in this trial including whether the level of residual leukaemia at the end of therapy is able to predict future relapse that would otherwise not be suspected. It is anticipated that the clinical trial will help define the most appropriate treatment strategies for children with leukaemia. This project, which is at the forefront of such studies worldwide, has major implications for the therapeutic management of children with leukaemia and has the potential of contributing directly to the improved survival of this most common of childhood cancers.