TREATMENT OF ACUTE LEUKEMIA

急性白血病的治疗

• 批准号: 3963304
• 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/3963304
• 关键词: bone marrow transplantation; cell differentiation; cellular immunity; central nervous system; child (0-11); circadian rhythms; combination cancer therapy; computed axial tomography; disease /disorder proneness /risk; drug metabolism; histochemistry /cytochemistry; human subject; human therapy evaluation; human tissue; lymphoblast; lymphocyte; lymphocytic leukemia; macrophage; methotrexate; monoclonal antibody; monocyte; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; nutrient intake activity; nutrition related tag; pediatric neoplasm /cancer; pharmacokinetics; purine nucleoside phosphorylase; tissue /cell culture

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, and 3) characterization of adverse sequelae of antileukemic therapy and design of treatment regimens which avoid them. The major ALL treatment protocol has successfully demonstrated that high-dose, protracted systemic methotrexate infusions can substitute for cranial radiation as central nervous system (CNS) preventive therapy for the majority of patients with ALL. Moreover, analysis of data derived from this study had 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. Studies on the bioavailability of orally administered maintenance chemotherapy have demonstrated that many patients do not achieve adequate drug levels in the blood, raising concern over this possible mechanism of treatment failure. A major, multi-institutional pharmacologic monitoring protocol has been instituted in an attempt to study the relationship between the bioavailability of orally administered maintenance chemotherapy and relapse in children with ALL. The role of diurnal variation, concomitant food intake and inter-patient variability in intracellular drug metabolism are being explored as possible factors in treament failure. Studies on late effects have demonstrated CT brain scan, neuroendocrine, and psychometric test abnormalities in long-term survivors of childhood ALL. These observations have stimulated the search for alternative, equally effective but less toxic methods of CNS preventive therapy.

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，以及 3) 抗白血病不良后遗症的特征 治疗和设计避免它们的治疗方案。 主要的 ALL 治疗方案已成功证明： 高剂量、长期全身甲氨蝶呤输注可以替代 颅脑放射作为中枢神经系统 (CNS) 预防性治疗 大多数 ALL 患者。 此外，对来自的数据进行分析 这项研究确定了一个具有中枢神经系统特殊风险的患者群体 复发。 已设计出一种新的高风险方案，试图 改善这些和其他低危患者的预后。 研究 口服维持化疗的生物利用度 表明许多患者在治疗期间没有达到足够的药物水平 血液，引起人们对这种治疗失败的可能机制的担忧。 一项主要的多机构药理学监测方案已经制定 旨在研究两者之间的关系 口服维持化疗的生物利用度和复发 患有 ALL 的儿童。 昼夜变化、伴随食物的作用 摄入量和患者间细胞内药物代谢的变异性 正在探索治疗失败的可能因素。 迟到的研究 效果已通过 CT 脑部扫描、神经内分泌和心理测量得到证实 儿童 ALL 长期幸存者的测试异常。 这些 观察刺激了对替代方案的寻找，同样有效 但毒性较小的中枢神经系统预防性治疗方法。