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）陈博士接受了良好的培训 实验室调查，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。 他已经过渡到转化临床研究的职业 在约翰·霍普金斯（Johns Hopkins）领导小儿骨髓移植程序。 他的 职业发展计划是获得理论和方法的正式培训 导致M.H.S.的临床研究学位，指导 佐治亚·沃格尔桑（Georgia Vogelsang）的指导，临床翻译研究。医学博士 血液系统恶性肿瘤分司临床主任。 史蒂文 M.D. Goodman，M.H.S.，博士，将担任拥有专业知识 流行病学，生物统计学和临床​​试验设计。 骨髓移植用于治疗不良普及恶性肿瘤和 取代有缺陷的造血细胞。 针对不良的儿童 实体瘤，外周血干细胞的使用大大降低了 BMT的发病率，并提供了执行双重BMT的机会 改善肿瘤控制。 然而。许多病原体较差的患者 实体瘤无法充分动员干细胞。 新的造血生长 对更原始细胞作用的因素可能会招募新的人群 造血细胞增强外周血干细胞收集。 这 由此产生的收藏可能具有不同的特性，包括更好 每个细胞的植入潜力。 该协议将比较动员 CD34 +细胞通过化学疗法 + G-CSF + SCF与化学疗法 + G-CSF，并将 在点头/SCID中的异种移植模型中测试其植入潜力 老鼠。 对于非恶性疾病的患者，骨髓的毒性 移植严重与可能的利益相比。 因此，毒性较小 必须开发移植疗法。 混合的供体嵌合可能足以 改善造血细胞的一些遗传疾病。 非母箭头 烧蚀性移植方案可在患者中产生混合嵌合 与传统骨髓相比，血液学恶性肿瘤的毒性要小得多 移植。 我们的假设是一种非箭头的方法可以是 适用于遗传疾病的患者，但需要增加 免疫抑制以克服完整免疫系统的障碍。 这 协议将使用持续的重新评估方法来查找最小剂量 在200个CGY TBI的背景下，氟达拉滨的of of fludarabine在 血红蛋白病的患者。