BONE MARROW TRANSPLANTATION FOR CHILDHOOD DISEASES

儿童疾病骨髓移植

• 批准号: 6027590
• 负责人: ALLEN R CHEN
• 金额: $ 13.08万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6027590
• 关键词: Ewing's tumor; NOD mouse; SCID mouse; adolescence (12-20); antineoplastics; bone marrow transplantation; child (0-11); clinical research; clinical trials; combination cancer therapy; fludarabine; hemoglobinopathy; homologous transplantation; human subject; human therapy evaluation; lymphoma; metastasis; neoplasm /cancer immunotherapy; neoplasm /cancer radiation therapy; neoplasm /cancer relapse /recurrence; pediatric neoplasm /cancer; radiation therapy dosage; stem cell factor; young adult human (21-34)

DESCRIPTION: (Applicant's Description) Dr. Chen is well trained in laboratory investigation, with a Ph.D. in immunology and postdoctoral research experience in the molecular biology of hematopoietic growth factor receptors. He has made the transition to a career in translational clinical research leading the pediatric bone marrow transplant program at Johns Hopkins. His career development plan is to obtain formal training in the theory and methods of clinical investigation leading to the M.H.S. degree, while conducting clinical translational research with mentorship from Georgia Vogelsang. M.D., Clinical Director of the Division of Hematologic Malignancies. Steven Goodman, M.D., M.H.S., Ph.D., will serve as co-mentor with expertise in epidemiology, biostatistics, and clinical trial design. Bone marrow transplantation is used to treat poor-prognosis malignancies and to replace defective hematopoietic cells. For children with poor-prognosis solid tumors, the use of peripheral blood stem cells substantially reduces the morbidity of BMT, and presents the opportunity to perform tandem BMTs to improve tumor control. However. many patients with poor-prognosis pediatric solid tumors fail to mobilize stem cells adequately. New hematopoietic growth factors that act on more primitive cells may recruit new populations of hematopoietic cells to augment peripheral blood stem cell collections. The resulting collections may have different properties, including better engraftment potential per cell. The protocol will compare mobilization of CD34+ cells by chemotherapy + G-CSF + SCF vs. chemotherapy + G-CSF, and will test their engraftment potential in a xenotransplantation model in NOD/SCID mice. For patients with nonmalignant diseases, the toxicity of bone marrow transplantation weighs heavily against its possible benefit. Thus, less toxic transplant therapy must be developed. Mixed donor chimerism may suffice to ameliorate some inherited diseases of hematopoietic cells. Non-marrow- ablative transplant regimens can produce mixed chimerism in patients with hematologic malignancies with much less toxicity than traditional bone marrow transplants. Our hypothesis is that a non-marrow-ablative approach can be adapted for patients with inherited disease, but will require an increase in immune suppression to overcome the barrier of an intact immune system. The protocol will use the continual reassessment method to find the minimum dose of fludarabine in the context of 200 cGy TBI to produce mixed chimerism in patients with hemoglobinopathies.

描述：（申请人的描述）陈博士受过良好的培训 实验室研究，拥有博士学位。免疫学和博士后研究 造血生长因子受体的分子生物学经验。 他已转向转化临床研究的职业生涯 领导约翰霍普金斯大学的儿科骨髓移植项目。 他的 职业发展计划是获得正规的理论和方法培训 临床研究导致 M.H.S.学位，同时进行 在 Georgia Vogelsang 的指导下进行临床转化研究。医学博士， 血液肿瘤科临床主任。 史蒂文 Goodman, M.D., M.H.S., Ph.D. 将担任联合导师，具有以下方面的专业知识 流行病学、生物统计学和临床​​试验设计。 骨髓移植用于治疗预后不良的恶性肿瘤 替换有缺陷的造血细胞。 对于预后不良的儿童 实体瘤中，外周血干细胞的使用大大减少了 BMT 的发病率，并提供了进行串联 BMT 的机会 改善肿瘤控制。 然而。许多儿科患者预后不良 实体瘤无法充分动员干细胞。 新造血细胞生长 作用于更原始细胞的因子可能会招募新的细胞群 造血细胞以增加外周血干细胞的收集。 这 生成的集合可能具有不同的属性，包括更好的属性 每个细胞的植入潜力。 该协议将比较动员 化疗 + G-CSF + SCF 对比化疗 + G-CSF 的 CD34+ 细胞，并且将 在 NOD/SCID 异种移植模型中测试它们的植入潜力 老鼠。 对于患有非恶性疾病的患者来说，骨髓的毒性 移植严重影响了其可能带来的益处。 因此毒性较小 必须开发移植疗法。 混合供体嵌合可能足以 改善造血细胞的一些遗传性疾病。 非骨髓- 消融移植方案可以在患者中产生混合嵌合状态 血液恶性肿瘤的毒性比传统骨髓低得多 移植。 我们的假设是非骨髓消融方法可以 适合患有遗传性疾病的患者，但需要增加 免疫抑制以克服完整免疫系统的屏障。 这 方案将使用持续重新评估方法来找到最小剂量 氟达拉滨在 200 cGy TBI 的背景下产生混合嵌合 血红蛋白病患者。