TREATMENT OF ACUTE LEUKEMIA

急性白血病的治疗

• 批准号: 3853239
• 负责人: D G POPLACK
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3853239
• 关键词: acute lymphocytic leukemia; antileukemic agent; cancer risk; central nervous system neoplasms; child (0-11); combination cancer therapy; drug adverse effect; human subject; human therapy evaluation; human tissue; methotrexate; molecular oncology; neoplasm /cancer genetics; neoplasm /cancer pharmacology; neoplasm /cancer relapse /recurrence; pediatric neoplasm /cancer; pharmacokinetics; phenotype; prognosis; tumor suppressor genes

Clinical research into the biology and treatment of acute leukemia is pursued with particular emphasis on acute lymphoblastic leukemia (ALL) of childhood. Major issues being addressed include: 1) development of therapeutic strategies aimed at improving overall prognosis of children with ALL, 2) investigation into the mechanisms of treatment failure with particular emphasis on evaluation of pharmacologic approaches to leukemic therapy, 3) characterization of adverse sequelae of antileukemic therapy and design of treatment regimens which avoid them, and 4) studies of the biology of ALL aimed at improving our basic understanding of the biology of this disease, identifying new diagnostic and prognostic tests and providing insight into the biologic basis for treatment failure. An earlier ALL treatment protocol demonstrated that high-dose, protracted systemic methotrexate infusions could substitute for cranial radiation as central nervous system (CNS) preventive therapy for the majority of patients with ALL. Analysis of data from this study also identified a patient group at particular risk for CNS relapse. A new, high risk protocol has been devised in an attempt to improve the prognosis for these and other poor risk patients. The results to date indicate that this therapy is highly effective in preventing both systemic and central nervous system relapses while avoiding the use of cranial radiation. In patients in the average risk category, a comparison of two forms of CNS preventive therapy (intrathecal vs high dose methotrexate) is under way. A major, multi-institutional pharmacologic monitoring protocol is in progress which is studying the relationship between the bioavailability of orally administered maintenance chemotherapy and relapse in children with ALL. Detailed analysis of the immunologic and molecular phenotype of acute lymphoblastic leukemia has led to the concept of a hierarchy of differentiation for both T cell and pre-B cell ALL. Studies are in progress to determine the relationship of molecular phenotype to prognosis. Evaluation of the P53 gene, a candidate tumor suppressor gene, suggests this gene may play a role in the pathogenesis of this disease.

急性白血病的生物学和治疗的临床研究 特别关注急性淋巴细胞白血病（ALL） 童年的。 正在解决的主要问题包括： 1） 旨在改善儿童总体预后的治疗策略 ALL，2）调查治疗失败的机制 特别强调药理学方法的评估 白血病治疗，3) 不良后遗症的特征 抗白血病疗法和避免它们的治疗方案的设计， 4) ALL 生物学研究旨在提高我们的基础 了解这种疾病的生物学，确定新的诊断方法 和预后测试，并提供对生物学基础的深入了解 治疗失败。 早期的 ALL 治疗方案表明，高剂量、 长期全身甲氨蝶呤输注可以替代颅内注射 放射作为中枢神经系统（CNS）预防性治疗 大多数 ALL 患者。 还对本研究的数据进行了分析 确定了中枢神经系统复发特别危险的患者群体。 一个新的、 高风险协议的设计是为了改善 这些和其他低危患者的预后。 迄今为止的结果 表明这种疗法对于预防这两种情况非常有效 全身和中枢神经系统复发，同时避免使用 颅脑辐射。 在平均风险类别的患者中， 两种中枢神经系统预防性治疗形式（鞘内注射与高位注射）的比较 剂量甲氨蝶呤）正在进行中。 一个大型、多机构 药理学监测方案正在进行中，正在研究 口服药物生物利用度之间的关系 ALL 儿童的维持化疗和复发。 详细的 急性感染的免疫学和分子表型分析 淋巴细胞白血病引发了等级制度的概念 T 细胞和前 B 细胞 ALL 的分化。 研究是在 确定分子表型与其关系的进展 预后。 候选抑癌基因 P53 基因的评估 基因，表明该基因可能在该疾病的发病机制中发挥作用 疾病。