CONSEQUENCES OF CNS PROPHYLAXIS IN CHILDREN WITH ALL

患有所有疾病的儿童中枢神经系统预防的后果

• 批准号: 3404101
• 负责人: DEBORAH P WABER
• 金额: $ 15.84万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1994-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3404101
• 关键词: acute leukemia; acute lymphocytic leukemia; central nervous system; child behavior disorders; child mental disorders; cognition disorders; combination cancer therapy; drug adverse effect; human subject; methotrexate; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; neoplasm /cancer radionuclide therapy; nervous system disorder diagnosis; neuropsychological tests; pediatric neoplasm /cancer; radiation sensitivity; radiation therapy dosage; radiobiology

Pediatric oncology has made remarkable strides in treating one of the most prevalent malignancies of childhood -- acute lymphoblastic leukemia (ALL). A diagnosis that was at one time nearly always fatal is now associated with a high probability for long-term disease-free survival. A major contributor to this high rate of success is central nervous system (CNS) treatment to prevent CNS leukemia. CNS treatment presents a difficult dilemma, however. The prognosis for long-term survival following a CNS relapse is poor; yet CNS treatment has been associated with significant compromise of physical and cognitive development. As prospects for long-term disease-free survival improve, therefore, the adverse consequences of treatment are of increasing medical concern. During the initial period of this grant, we determined whether certain children are at greater risk for adverse effects of CNS treatment by virtue of their age and sex. In the proposed continuation, we will determine (1) whether specific treatment agents are differentially toxic depending on dose levels or their use in combination with one another; and (2) whether the effects of treatment are uniform or whether different aspects of development (e.g., growth, cognition) are differentially sensitive to specific treatment agents. A key aim of the research will be to determine whether application of a hyperfractionation schedule to deliver cranial irradiation (XRT) can reduce toxicity without sacrificing efficacy. Two studies are planned, one retrospective and one prospective, in which neurobehavioral development and bone growth will be assessed in these children. Specific treatments to be evaluated will be cranial radiation therapy (delivered in standard fractions or a hyperfractionation schedule) and intravenous methotrexate therapy (standard-dose and high-dose). The data to be generated will be important not only for computing the relative risks and benefits of treatment alternatives, but also for providing any early intervention that may be able to ameliorate possible adverse effects where no equally efficacious but less toxic alternative exists.

儿科肿瘤学在治疗其中一种疾病方面取得了显着进展 儿童期最常见的恶性肿瘤——急性淋巴细胞白血病 （全部）。 曾经几乎总是致命的诊断现在变成了 与长期无病生存的高概率相关。 如此高成功率的一个主要贡献者是中枢神经 系统（中枢神经系统）治疗以预防中枢神经系统白血病。 中枢神经系统治疗呈现 然而，这是一个困难的困境。 长期生存的预后 中枢神经系统复发后效果较差；但中枢神经系统治疗已与 严重损害身体和认知发展。 作为 长期无病生存的前景改善，因此， 治疗的不良后果日益受到医学关注。 在这笔赠款的初始阶段，我们确定了某些 儿童遭受中枢神经系统治疗不良反应的风险更大 由于他们的年龄和性别。 在拟议的延续中，我们将 确定（1）特定治疗剂是否具有不同的毒性 取决于剂量水平或它们彼此组合使用； (2)治疗效果是否均匀或是否 发展的不同方面（例如成长、认知） 对特定治疗药物的敏感性不同。 该计划的一个关键目标是 研究将确定是否应用 进行颅脑照射 (XRT) 的超分割计划可以 减少毒性而不牺牲功效。 计划进行两项研究， 一项回顾性和一项前瞻性，其中神经行为 将评估这些儿童的发育和骨骼生长。 待评估的具体治疗方法将是颅脑放射治疗 （以标准分割或超分割方案提供）和 静脉注射甲氨蝶呤治疗（标准剂量和高剂量）。 要生成的数据不仅对于计算很重要 治疗替代方案的相对风险和益处，也适用于 提供任何可能能够改善可能的早期干预 没有同样有效但毒性较小的替代品的不良反应 存在。