AUTOLOGOUS BONE MARROW TRANSPLANTATION FOR HEMATOLOGIC MALIGNANCY

自体骨髓移植治疗血液恶性肿瘤

• 批准号: 3729930
• 负责人: STEPHEN J FORMAN
• 金额: --
• 依托单位: CITY OF HOPE NATIONAL MEDICAL CENTER
• 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/3729930
• 关键词: CD antigens; Hodgkin's disease; acute lymphocytic leukemia; autologous transplantation; bone marrow transplantation; chromosome translocation; clinical trials; hematopoietic stem cells; human subject; human therapy evaluation; neoplasm /cancer radionuclide therapy; neoplasm /cancer relapse /recurrence; neoplasm /cancer remission /regression; pharmacokinetics; ribozymes; serology /serodiagnosis; statistics /biometry; urinalysis; yttrium

The goal of our study is to improve disease-free survival and overall survival in patients with hematologic malignancies through the use of high dose therapy and autologous stem cell grafting. It is the intent to introduce novel approaches designed to increase the efficacy and potential safety of high dose chemotherapy or chemoradiotherapy and stem cell support for patients who are undergoing treatment for refractors B cell lymphoma, Hodgkin's disease and leukemia. These innovations include using high dose sequential chemotherapy for the treatment of relapsed Hodgkin's disease and the use of yttrium labeled monoclonal antibodies to the CD20 antigen as part of the preparatory regimen for patients undergoing autologous bone marrow transplantation (BMT) for B cell lymphoma. We will also study the feasibility, effectiveness and toxicity of adding yttrium labeled monoclonal antibodies to either the CD33 or CD45 antigen in patients undergoing autologous BMT as treatment for acute myelogenous leukemia and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). In addition, in this project we will investigate the use of a nw vector, an adeno-associated virus for efficient transduction of hematopoietic stem cells. This approach is designed to elucidate the pattern and degree of hematopoietic and immune reconstitution, as well as the potential cause of relapse that occurs after autologous BMT for patients undergoing treatment for low grade lymphoma following radiation and non-radiation containing regimens. We will also study the use of a ribozyme designed to cleave the hybrid RNA that results from the t (9;22) chromosome translocation of Ph+ ALL with the goal to purge peripheral blood stem cells of leukemia in patients undergoing autologous BMT for this disorder. These studies will test novel methods designed to decrease the major problem of relapse, which is the greatest obstacle to successful use of autologous stem cell transplant for treatment of malignant lymphomas, Hodgkin's disease, and acute leukemia. The project focuses on modifying the preparatory regimen to treat the residual body burden of malignancy, a well as developing molecular methods designed to purge the stem cell product of contaminating leukemia cells. Finally, Project 2 will serve as a clinical resource for experimental Projects.

我们研究的目的是改善无疾病的生存和整体 血液系统恶性肿瘤患者的生存性通过高 剂量疗法和自体干细胞嫁接。 这是意图 引入旨在提高功效和潜力的新颖方法 高剂量化疗或化学放疗和干细胞支持的安全性 对于正在接受折射剂B细胞淋巴瘤治疗的患者 霍奇金病和白血病。 这些创新包括使用高剂量顺序化学疗法进行 霍奇金病的复发和标记的YTTrium的使用 作为预备的一部分，与CD20抗原的单克隆抗体 接受自体骨髓移植的患者的方案 （BMT）用于B细胞淋巴瘤。 我们还将研究可行性， 添加Yttrium标记为单克隆抗体的有效性和毒性 接受自体BMT的患者的CD33或CD45抗原As 治疗急性粒细胞性白血病和费城染色体 阳性（pH+）急性淋巴细胞白血病（全部）。 另外，在此 项目我们将调查使用NW矢量的使用，这是腺相关的 有效转导造血干细胞的病毒。 这 方法旨在阐明造血的模式和程度 和免疫机构，以及复发的潜在原因 在自体BMT之后发生，接受低级治疗的患者 辐射和非辐射含有方案后的淋巴瘤。 我们 还将研究用于裂解杂交RNA的核酶的使用 这是由p（9; 22）pH+的染色体易位的结果 清除患者白血病外周血干细胞的目标 患有这种疾病的自体BMT。 这些研究将测试旨在减少主要的新方法 复发问题，这是成功使用的最大障碍 自体干细胞移植用于治疗恶性淋巴瘤， 霍奇金病和急性白血病。 该项目的重点是修改 治疗残留身体负担的预科治疗方案， 以及开发旨在清除干细胞的分子方法 污染白血病细胞的产物。 最后，项目2将作为 实验项目的临床资源。