BONE MARROW TRANSPLANTATION FOR CHILDHOOD DISEASES

描述：(申请人的描述)陈博士受过良好的 实验室调查，免疫学博士和博士后研究 在造血生长因子受体的分子生物学方面的经验。 他已经转行从事转化型临床研究。 在约翰霍普金斯大学领导儿科骨髓移植项目。他的 职业发展计划是获得正规培训的理论和方法 临床研究导致M.H.S.学位，同时进行 乔治亚沃格桑指导下的临床转化研究。医学博士， 恶性血液病科临床主任。史蒂文 Goodman，M.D.，M.H.S.，Ph.D.将担任共同导师，拥有以下专业知识 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和 以替换有缺陷的造血细胞。对于预后不佳的儿童 对于实体瘤，外周血干细胞的使用大大降低了 骨髓移植的发病率，并提供了进行串联骨髓移植的机会 提高肿瘤控制水平。然而。许多预后不良的儿科患者 实体瘤不能充分动员干细胞。新的造血细胞生长 作用于更原始细胞的因子可能会招募新的 增加外周血干细胞采集的造血细胞。这个 产生的集合可能具有不同的属性，包括更好的 每个细胞的嫁接潜力。该议定书将比较动员 化疗+G-CSF+SCF与化疗+G-CSF的CD34+细胞，并将 在NOD/SCID异种移植模型中检测它们的植入能力 老鼠。 对于非恶性疾病的患者，骨髓的毒性 移植与其可能带来的好处相比，有很大的权衡。因此，毒性较小 必须开发移植疗法。混合供体嵌合体可能足以 改善某些遗传性造血细胞疾病。非骨髓- 消融性移植方案可在慢性粒细胞白血病患者中产生混合嵌合体 比传统骨髓毒性小得多的恶性血液病 移植。我们的假设是，一种非骨髓切除的方法可以 适用于遗传性疾病患者，但需要增加 免疫抑制以克服完整免疫系统的障碍。这个 方案将使用持续重新评估的方法来寻找最小剂量 在200cGyTBI的背景下产生混合嵌合体的氟达拉滨 患有血红蛋白疾病的患者。

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.