DETECTION AND THERAPY OF RESIDUAL LEUKEMIA IN CHILDREN

描述：（申请人的摘要）尽管提高了治愈率， 儿童急性淋巴细胞白血病（ALL），占所有患者的25-30% 最终死于疾病 的长期目标 拟议的研究是为了改善这部分患者的临床结果。 通过早期识别可能复发的患者， 可能以更及时的方式激发潜在的治愈性治疗， 从而提高长期存活者的比例。 这一目标将 通过三个相互关联的项目进行。 第一，过度表达 WT 1和BCL-2基因的表达将被评估为最小残留的标志物 儿童ALL患者的MRD。 潜在的假设是， 这两个指标与白血病的相关性比目前更广泛， 标志物，并将大大扩大未来的能力， 识别高危患者。 第2章寻求扩张 上一个支助期间取得的成果表明， MRD的免疫学监测在评估 儿童ALL患者 连续骨髓中的免疫学发现 将比较来自B和T系ALL患者的样本与事件 无生存期，以及临床和生物学风险特征， 建立本试验的独立预测强度。 数据将 还提供了与WT 1结果进行交叉比较的机会， 在特定目标1中进行BCL-2筛查。 基于令人鼓舞的初步 结果，特定目标3中的研究试图评估 使用外周血代替骨髓进行MRD研究。 成功 在这项奋进将从根本上改善缓解研究的患者， 所有，通过克服顺序所造成的实际和道德约束， 儿童骨髓穿刺 MRD的临床意义 由于缺乏对一大群人的前瞻性研究， 统一对待患者。 本申请中提出的研究应 满足需要并证明临床管理的可行性 根据ALL儿童的MRD检测做出决定。

DESCRIPTION: (Applicant's Abstract) Despite advancing cure rates in childhood acute lymphoblastic leukemia (ALL), 25-30% of all patients eventually succumb to their disease. The long-term objective of the proposed research is to improve clinical outcome in this subset of patients. By early identification of patients who are likely to relapse, it should be possible to instigate potentially curative therapy in a more timely manner, thus boosting the proportion of long term survivors. This goal will be pursued through three interrelated projects. In the first, overexpression of WT1 and BCL-2 genes will be assessed as markers of minimal residual disease (MRD) in childhood ALL patients. The underlying hypothesis is that these two indicators are more widely associated with leukemia than current markers, and will significantly expand capabilities for prospective identification of high risk patients. Specific Aim 2 seeks to expand results obtained during the previous period of support, suggesting that immunologic monitoring of MRD has clinical utility in the assessment of childhood ALL patients. Immunologic findings in sequential bone marrow samples from patients with B- and T-lineage ALL will be compared with event free survival, as well as presenting clinical and biologic risk features, to establish the independent predictive strength of this assay. The data will also provide opportunities for cross comparisons with results of WT1 and BCL-2 screening in Specific Aim 1. Based on encouraging preliminary results, studies in Specific Aim 3 seek to assess the clinical utility of MRD investigations using peripheral blood instead of bone marrow. Success in this endeavor will radically improve remission studies in patients with ALL, by overcoming the practical and ethical constraints posed by sequential bone marrow aspirations in children. The clinical significance of MRD has been in doubt because of the lack of prospective studies in a large group of uniformly treated patients. The studies proposed in this application should meet that need and demonstrate the feasibility of clinical management decisions based on MRD detection in children with ALL.