TREATMENT OF ACUTE LEUKEMIA

急性白血病的治疗

• 批准号: 3874476
• 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/3874476
• 关键词: acute leukemia; acute lymphocytic leukemia; antileukemic agent; cancer prevention; cancer risk; cell differentiation; cellular oncology; central nervous system; central nervous system neoplasms; child (0-11); combination cancer therapy; computed axial tomography; cytokine receptors; disease /disorder proneness /risk; dosage; drug adverse effect; drug metabolism; hematopoietic stem cells; human subject; human therapy evaluation; human tissue; interleukin 2; leukocyte activation /transformation; lymphocytic leukemia; methotrexate; neoplasm /cancer chemotherapy; neoplasm /cancer classification /staging; neoplasm /cancer genetics; neoplasm /cancer immunotherapy; neoplasm /cancer pharmacology; neoplasm /cancer radiation therapy; pediatric neoplasm /cancer; pharmacokinetics; tissue /cell culture; 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 a future. 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 patient 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 ris patients. The results to date indicate that this therapy is highly effectiv 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 molecula 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 重点关注急性淋巴细胞白血病（ALL） 童年。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 特别强调白血病药理学方法的评估 治疗，3) 抗白血病治疗不良后遗症的特征 并设计避免它们的治疗方案，以及 4) 研究 ALL 生物学旨在提高我们对 ALL 生物学的基本了解 这种疾病，确定新的诊断和预后测试并提供 洞察未来的生物学基础。 早期的 ALL 治疗方案表明，高剂量、长期治疗 全身甲氨蝶呤输注可以替代颅脑放疗 大多数患者的中枢神经系统（CNS）预防性治疗 与所有。这项研究的数据分析还确定了一个患者组 中枢神经系统复发的风险特别高。一种新的高风险方案已经 旨在改善这些和其他不良风险的预后 患者。迄今为止的结果表明，这种疗法非常有效 在预防全身和中枢神经系统复发的同时 避免使用颅脑辐射。在平均风险的患者中 类别，两种中枢神经系统预防性治疗形式（鞘内注射）的比较 与高剂量甲氨蝶呤相比）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 口服维持药物的生物利用度之间的关系 ALL 儿童的化疗和复发。详细分析 急性淋巴细胞白血病的免疫学和分子表型 T 细胞和前 B 细胞分化层次的概念 细胞全部。正在进行研究以确定分子之间的关系 表型对预后的影响。候选肿瘤 P53 基因的评估 抑制基因，表明该基因可能在发病机制中发挥作用 这种病。