DETECTION AND THERAPY OF RESIDUAL LEUKEMIA IN CHILDREN

儿童残留白血病的检测和治疗

• 批准号: 6350136
• 负责人: DARIO CAMPANA
• 金额: $ 21万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6350136
• 关键词: CD antigens; acute lymphocytic leukemia; bone marrow; cancer risk; child (0-11); clinical research; flow cytometry; fluorescence microscopy; gene expression; genetic markers; human subject; human therapy evaluation; immunologic assay /test; karyotype; minimal residual disease; neoplasm /cancer relapse /recurrence; neoplasm /cancer therapy; neoplastic cell; pediatric neoplasm /cancer; phenotype; polymerase chain reaction; prognosis; protooncogene

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.

描述：（申请人的摘要）尽管治愈率有所提高 儿童急性淋巴细胞白血病 (ALL)，占所有患者的 25-30% 最终死于他们的疾病。 该组织的长期目标 拟议的研究旨在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， 可能更及时地启动潜在的治愈性治疗， 从而提高长期幸存者的比例。 这个目标将是 通过三个相互关联的项目来实现。 首先，过度表达 WT1 和 BCL-2 基因将被评估为最小残留标记 儿童 ALL 患者的疾病（MRD）。 基本假设是 这两个指标与白血病的相关性比目前的指标更广泛 标记，并将显着扩展未来的能力 识别高风险患者。 具体目标 2 寻求扩展 上一时期的支持期间获得的结果表明 MRD 的免疫学监测在评估 儿童所有患者。 连续骨髓的免疫学发现 B 系和 T 系 ALL 患者的样本将与事件进行比较 自由生存，以及呈现临床和生物学风险特征，以 建立该测定的独立预测强度。 数据将 还提供了与 WT1 和 WT1 结果进行交叉比较的机会 具体目标 1 中的 BCL-2 筛查。基于令人鼓舞的初步结果 结果，具体目标 3 中的研究旨在评估以下方法的临床效用： MRD 研究使用外周血而不是骨髓。 成功 这一努力将从根本上改善患者的缓解研究 ALL，通过克服顺序带来的实践和道德限制 儿童骨髓愿望。 MRD的临床意义 由于缺乏大量前瞻性研究而受到质疑 统一治疗的患者。 本申请中提出的研究应 满足该需求并证明临床管理的可行性 基于 ALL 儿童 MRD 检测的决策。