CONSEQUENCES OF CNS PROPHYLAXIS IN CHILDREN WITH ALL

儿科肿瘤学在治疗其中一种 儿童最常见的恶性肿瘤--急性淋巴细胞白血病 （全部）。 曾经几乎总是致命的诊断现在 与长期无病生存的高概率相关。 一个主要的贡献者，这一高成功率是中枢神经系统 中枢神经系统（CNS）治疗，以预防中枢神经系统白血病。 CNS治疗呈现 然而，这是一个两难的问题。 长期生存的预后 中枢神经系统复发后的预后差;然而，中枢神经系统治疗与 对身体和认知发育都有很大影响 作为 长期无病生存的前景改善，因此， 治疗的不良后果越来越受到医学关注。 在此期间，我们确定是否有某些 儿童CNS治疗的不良反应风险更大， 因为他们的年龄和性别。 在拟议的延续中，我们将 确定（1）特定治疗剂是否具有不同毒性 取决于剂量水平或它们彼此组合使用; 以及（2）治疗效果是否一致，或者 开发的不同方面（例如，增长，认知） 对特定治疗剂的敏感性差异。 一个关键的目标， 研究将确定是否应用 递送颅照射（XRT）超分割时间表可以 在不牺牲功效的情况下降低毒性。 计划进行两项研究， 一个是回顾性的，一个是前瞻性的， 将对这些儿童的发育和骨骼生长进行评估。 具体的治疗方法将进行评估，颅放射治疗 （以标准分数或超分数时间表递送）和 静脉内甲氨蝶呤治疗（标准剂量和高剂量）。 要生成的数据不仅对计算 治疗替代品的相对风险和效益， 提供任何早期干预措施， 如果没有同等有效但毒性较低的替代品， 存在.

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.