BONE MARROW TRANSPLANTATION FOR CHILDHOOD DISEASES

描述：（申请人的描述）陈博士在以下方面受过良好的培训： 实验室研究，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职业 在约翰霍普金斯领导儿科骨髓移植项目 他 职业发展计划是获得正规培训的理论和方法 导致M.H.S.的临床研究度，同时进行 临床转化研究与导师从格鲁吉亚Vogelsang。医学博士， 血液肿瘤科临床主任。 史蒂文 古德曼医学博士M.H.S.，博士，将担任共同导师， 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， 来替换有缺陷的造血细胞 对于预后不良的儿童 在实体瘤中，外周血干细胞的使用大大减少了肿瘤的发生。 BMT的发病率，并提出了进行串联BMT的机会， 改善肿瘤控制。 然而.许多儿科预后不良的患者 实体瘤不能充分动员干细胞。 新造血生长 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。 的 结果集合可能具有不同的属性，包括更好的 每个细胞的植入潜力。 本方案将比较 化疗+ G-CSF + SCF与化疗+ G-CSF的CD 34+细胞， 在NOD/SCID异种移植模型中测试它们的植入潜力 小鼠 对于非恶性疾病患者， 移植与其可能带来的益处相比显得很重要。 因此，毒性较小 必须发展移植疗法。 混合供体嵌合体可能足以 改善造血细胞的某些遗传性疾病。 非骨髓- 消融性移植方案可在患有以下疾病的患者中产生混合嵌合体 血液恶性肿瘤，毒性比传统骨髓低得多 移植 我们的假设是，非骨髓切除方法可以 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屏障。 的 方案将使用持续再评估方法来确定最小剂量 氟达拉滨在200 cGy TBI的背景下产生混合嵌合体， 血红蛋白病患者。

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.