PILOT STUDY OF DOSE INTENSIFIED PROCARBAZINE, CCNU, VINCRISTINE FOR BRAIN TUMORS

新诊断的“预后不良”脑肿瘤患者和 患有复发性脑肿瘤的患者，既往未接受过化疗， 全脑脊髓放射治疗4个疗程 丙卡巴肼、环己亚硝脲和阿托伐他汀组成的压缩化疗 ）PCV）。 将通过单采术采集外周血干细胞 在治疗前进行手术，并在每次手术后返回给患者 化疗疗程。 增加骨髓对 化疗药物，我们建议收集一部分外周血 将从中分离CD 34+细胞的造血干细胞， 用人O 6-甲基鸟嘌呤DNA甲基转移酶（MGMT）转导c 逆转录病毒构建体中的DNA，PGK-MGMT。 这些细胞，将被给予 在化疗疗程后返回给患者，并且沿着 未经处理的干细胞，在疗程#4之后。只有未经处理的干细胞 将在疗程#2和#3后返还给患者。 这是一 非清髓性方案和大量输注 每个周期中未操作的单核细胞最大限度地降低了 植入不良。 主要目的包括：1）确定毒性 与输注转导了CD 34+衍生细胞相关， 表达O 6-甲基鸟嘌呤DNA甲基转移酶的逆转录病毒载体; 2） 为了确定在美国进行的细胞遗传修饰的安全性， 重组纤连蛋白片段CH-296存在，用于 协助逆转录病毒进入哺乳动物细胞; 3）确定任何 在逆转录病毒期间暴露于CH-296的细胞植入的证据 转导; 4）确定以下FN抗体的证据： 在离体逆转录病毒期间输注暴露于CH-296的细胞 转导

Patients with newly diagnosed "poor prognosis" brain tumors and patients with recurrent brain tumors who have received no prior chemotherapy and no craniospinal radiation therapy will treated with 4 courses of time compressed chemotherapy composed of Procarbazine, CCNU and Vincristine )PCV). Peripheral blood stem cells will be collected by an apheresis procedure prior to treatment and given back to the patient following each course of chemotherapy. To increase the tolerablility of the marrow to the chemotherapy drugs, we propose to collect a portion of the peripheral blood stem cells from which the CD34+ cells will be separated and transduced with the human O6-methylguanine DNA methyltransferase (MGMT) c DNA in the retrovirus construct, PGK-MGMT. These cells, will be given back to the patient following chemothapy courses, and along with unmanipulated stem cells, after course #4. Only unmanipulated stem cells will be given back to the patient following courses #2 and #3. This is a non-myeloablative protocol and the infusion of large number of unmanipulated mononuclear cells during each cycle minimizes the risk of poor engraftment. The primary objectives include the following 1) to determine toxcity associated with infusion of CD34+ derived cells transduced with a retroviral vector expressing O6-methylguanine DNA methyltransferase; 2) to determine the safety of genetic modification of cells carried out in the presence of recombinant fibronectin fragment, CH-296, utilized to assist in retroviral entry into mammalian cells; 3) to determine any evidence of engraftment of cells exposed to CH-296 during retroviral transduction; 4) to determine evidence of antibodies to FN following infusion of cells exposed to CH-296 during ex vivo retroviral transduction.