TREATMENT OF ACUTE LEUKEMIA

急性白血病的治疗

• 批准号: 3838114
• 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/3838114
• 关键词: 6 thioguanine; 6 thiopurine; acute lymphocytic leukemia; antileukemic agent; central nervous system neoplasms; child (0-11); drug adverse effect; human subject; human therapy evaluation; methotrexate; neoplasm /cancer chemotherapy; neoplasm /cancer diagnosis; neoplasm /cancer genetics; neoplasm /cancer pharmacology; neoplasm /cancer relapse /recurrence; oral administration; pediatric neoplasm /cancer; pharmacokinetics; polymerase chain reaction; prognosis; thiopurine; 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 subsequent, high risk protocol was devised to improve the prognosis for these and other poor risk patients. The results of that study indicated that the therapy was highly effective in preventing both systemic and central nervous system relapses while avoiding the use of cranial radiation. A new protocol for high risk patients is attempting to demonstrate that dose intensification, accomplished through the concomitant use of G-CSF, will improve the prognosis for this patient group. In this study molecular analysis (pcr) will be performed to evaluate minimal residual disease. A major, multi-institutional pharmacologic monitoring protocol which has studied the relationship between the bioavailability of orally administered maintenance chemotherapy and relapse in children with ALL has recently been completed and the results are being analyzed. Study of the clinical pharmacology of the thiopurines, mercaptopurine and thioguanine, has led to the development of new therapeutic approaches with these agents. Several new intrathecal chemotherapy approaches have been developed to provide new therapy for patients with central nervous system leukemia. Collaborative studies are evaluating the role of the P53 gene, a candidate tumor suppressor gene, 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生物学的基本了解 这种疾病，确定新的诊断和预后测试和 提供对治疗失败的生物学基础的深入了解。 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 大多数人的中枢神经系统（CNS）预防性治疗 ALL 患者。 对本研究数据的分析还发现 中枢神经系统复发特别危险的患者群体。 随后的高 设计风险方案是为了改善这些和其他疾病的预后 低危患者。 该研究结果表明该疗法 对预防全身和中枢神经系统非常有效 系统复发，同时避免使用颅脑辐射。 一个新的 针对高风险患者的方案正试图证明剂量 通过同时使用 G-CSF 来实现强化，将 改善该患者组的预后。 在本研究中分子 将进行分析（PCR）以评估微小残留病。 一个 主要的多机构药理学监测方案 研究了口服生物利用度之间的关系 ALL 儿童的维持化疗和复发 最近已完成，正在分析结果。 研究 硫嘌呤类药物、巯基嘌呤类药物的临床药理学 硫鸟嘌呤，导致了新治疗方法的开发 与这些代理。 几种新的鞘内化疗方法 为中枢神经系统疾病患者提供新的治疗方法 系统性白血病。 合作研究正在评估 P53基因，候选抑癌基因，在本病发病机制中的作用 疾病。