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

使用微小残留病检测来改善儿童急性淋巴细胞白血病的治疗结果

• 批准号: nhmrc : 209599
• 负责人: Prof Glenn Marshall
• 金额: $ 21.11万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/use-minimal-residual-lymphoblastic-leukaemia/96666
• 关键词: use; Minimal; Residual; Disease; detection

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. Available evidence 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. The failure to respond well to treatment is assessed by a novel molecular genetic technique developed in our laboratory that can detect and quantitate very low levels of residual leukaemia with great sensitivity and specificity. The major goal of this project is to conduct a clinical trial in which this testing procedure is used at an early stage of treatment, and patients who have a bad result on this test, will be given more intensive treatment to see if this improves survival rates. In addition, the project is also directed towards investigating a range of genes known to have a role in drug detoxification. A number of naturally occurring variations exist for these drug metabolising genes and there is evidence suggesting that specific variations or patterns may influence a cancer's response to treatment. We will therefore examine the genetic patterns present in a large cohort of leukaemias and correlate these patterns with response to treatment. It is anticipated that these studies will help define the most appropriate treatment strategies for children with leukaemia. This project therefore 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.

白血病是最常见的儿童癌症，约占所有病例的35%。尽管进行了强化治疗，但这种疾病经常在骨髓中复发，尽管儿童在诊断时根据一些标准被分为预后良好和预后不良组，但两组都有复发。现有证据表明，在其他预后良好的组中早期发现不良治疗反应，并在癌症负荷处于低水平时实施替代疗法，很有可能改善患者生存率。对治疗反应不佳的患者通过我们实验室开发的一种新的分子遗传技术进行评估，该技术可以检测和定量非常低水平的残留白血病，具有很高的灵敏度和特异性。该项目的主要目标是进行一项临床试验，在该试验中，在治疗的早期阶段使用该测试程序，并且在该测试中结果不佳的患者将接受更强化的治疗，以观察这是否会提高生存率。此外，该项目还旨在调查已知在药物解毒中发挥作用的一系列基因。这些药物代谢基因存在许多自然发生的变异，有证据表明特定的变异或模式可能影响癌症对治疗的反应。因此，我们将研究存在于一个大型队列白血病的遗传模式，并将这些模式与治疗反应相关联。预计这些研究将有助于确定白血病儿童最合适的治疗策略。因此，该项目对白血病儿童的治疗管理具有重大意义，并有可能直接有助于提高这一最常见的儿童癌症的生存率。