TREATMENT OF ACUTE LEUKEMIA

急性白血病的治疗

• 批准号: 3916638
• 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/3916638
• 关键词: B lymphocyte; T lymphocyte; antibody receptor; antileukemic agent; cell differentiation; cellular oncology; central nervous system; child (0-11); combination cancer therapy; computed axial tomography; disease /disorder proneness /risk; dosage; drug adverse effect; drug metabolism; hematopoietic stem cells; human subject; human therapy evaluation; interleukin 1; lymphocytic leukemia; methotrexate; molecular oncology; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplasm /cancer radiation therapy; pediatric neoplasm /cancer; pharmacokinetics; radioprotective agents; 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. 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 beer 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. On the basis of in vitro studies indicating that Interleukin-2 will induce phenotypic and functional maturation in acute lymphoblastic leukemia cells, a Phase I study of this potential antileukemic approach is being instituted. A study demonstrating expression of the 8 IL-2 receptor on hematopoietic malignant cells offers a potential avenue for future therapy. 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.

急性白血病生物学和治疗的临床研究 特别强调急性淋巴细胞白血病 （全部）童年。 正在解决的主要问题包括：1） 制定旨在改善整体的治疗策略 ALL 儿童的预后，2) 调查 治疗失败的机制，特别强调 白血病治疗药理学方法的评估，以及 3) 抗白血病治疗不良后遗症的特征和 设计避免它们的治疗方案。 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 颅脑放射作为中枢神经系统 (CNS) 的预防作用 为大多数 ALL 患者提供治疗。 数据分析 这项研究还确定了一个处于特殊风险的患者群体 用于中枢神经系统复发。 啤酒设计了一种新的高风险协议 尝试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 有效预防全身和中枢神经系统 在避免使用颅脑辐射的同时复发。 在患者中 在平均风险类别中，两种形式的 CNS 的比较 预防性治疗（鞘内注射与高剂量甲氨蝶呤）正在进行中 方式。 主要的、多机构的药理学监测 协议正在进行中，正在研究之间的关系 口服维持化疗的生物利用度 以及患有 ALL 的儿童复发。 基于体外研究 表明Interleukin-2会诱导表型和功能 急性淋巴细胞白血病细胞的成熟，一项 I 期研究 这种潜在的抗白血病方法的研究正在制定中。 一个 研究表明 8 IL-2 受体的表达 造血恶性细胞为未来提供了潜在的途径 治疗。 免疫学和分子学的详细分析 急性淋巴细胞白血病的表型引发了这一概念 T 细胞和前 B 细胞的分化层次 全部。