CONSEQUENCES OF CNS PROPHYLAXIS IN CHILDREN WITH ALL

儿科肿瘤学在治疗一种 儿童最常见的恶性肿瘤--急性淋巴细胞性白血病 (全部)。一种曾经几乎总是致命的诊断现在成了致命的 与长期无病存活的可能性很高有关。 这一高成功率的一个主要因素是中枢神经系统 系统(CNS)治疗，以预防CNS白血病。中枢神经系统治疗报告 然而，这是一个艰难的两难境地。长期生存的预后 中枢神经系统复发后情况不佳；然而中枢神经系统治疗与 在身体和认知发展方面有显著的妥协。AS 因此，长期无病生存的前景有所改善 治疗的不良后果日益引起医学界的关注。 在这笔赠款的最初阶段，我们确定了某些 儿童接受中枢神经系统治疗的不良反应的风险更大 他们的年龄和性别的优点。在拟议的延续中，我们将 确定(1)特定处理剂是否具有不同的毒性 取决于剂量水平或它们相互结合使用； (2)治疗效果是否一致或是否一致 发展的不同方面(例如，成长、认知)是 对特定的治疗药物具有不同的敏感性。该计划的一个主要目标 研究将确定是否应用 超分割颅脑照射计划(XRT)罐头 在不牺牲疗效的情况下降低毒性。计划进行两项研究， 一次回顾，一次前瞻性，其中神经行为 将对这些儿童的发育和骨骼生长进行评估。 有待评估的具体治疗方法是颅脑放射治疗。 (以标准分数或超分割时间表提供)和 甲氨蝶呤静脉治疗(标准剂量和大剂量)。 要生成的数据不仅对于计算 治疗替代方案的相对风险和收益，但也包括 提供任何可能改善的早期干预措施 没有同样有效但毒性较低的替代品的不良影响 是存在的。

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.