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

点击翻译按钮获取中文摘要

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.