Sibling Donor Cord Blood Banking and Transplantation

兄弟姐妹捐献者脐带血储存和移植

• 批准号: 6656242
• 负责人: Bertram Harold Lubin
• 金额: $ 128.56万
• 依托单位: CHILDREN'S HOSPITAL & RES CTR AT OAKLAND
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6656242
• 关键词: adolescence (12-20); artificial immunosuppression; blood banks; busulfan; child (0-11); clinical trials; cooperative study; cord blood; cyclophosphamide; cyclosporines; fludarabine; human subject; human therapy evaluation; mycophenolate mofetil; patient oriented research; siblings; sickle cell anemia; stem cell transplantation; thalassemia

DESCRIPTION (provided by applicant): Hematopoietic stem cell transplantation (HSCT) has become an important treatment option for patients with sickle cell anemia or thalassemia. While the source of HSCT is usually bone marrow from an HLA identical sibling, cord blood (CB) may prove to be an important resource. CB can contain sufficient numbers of hematopoietic stem cells for engraftment post myeloablative therapy, can be used without a complete HLA match, and CB has less chance of inducing graft-versus-host disease (GVHD) than bone marrow. To increase the availability of CB for these purposes, a number of CB banks have been developed. However, none have focused on sibling donor cord blood (SDCB) collection, a process which requires a unique set of procedures to accommodate collection at remote sites, and none have extensive experience working with families who have a child with sickle cell anemia or thalassemia. This revised application contains two specific aims: (1) to collect sibling-donor CB in families that currently have a child with sickle cell anemia or thalassemia and (2) to use these CBs to conduct the first multi-center prospective pilot study of CB transplantation in children with these two diseases. The SDCB Program at CHORI will follow procedures that comply with standards for cord blood banking. The success of our feasibility study has demonstrated that our program can collect a sufficient number of Cbs to conduct the pilot transplantation study. Scientific questions regarding engraftment failure, disease recurrence, HLA compatibility, and the requirement for a critical number of HSCs are addressed in the application. We will test the hypothesis that a novel immunosuppressive conditioning regimen (fludarabine, cyclophosphamide and busulfan) and post transplant therapy (mycophenalate mofetil and cyclosporine) will improve engraftment rates and prevent disease recurrence. The effect of SDCB transplantation on hematologic parameters and GVHD will be monitored. Information for this pilot study will be used to design new approaches employing SDCB transplantation for patients with hemoglobinopathies. In summary, the ultimate goal of our proposal will be to focus our SDCB program on collection of CBs from families that have a child with a hemoglobinopathy and to use these CBs to evaluate the role of CB transplants in these children. We anticipate that our project will advance the field of SDCB transplantation from case reports to clinical investigation and, will provide a rational basis for further studies of CB transplantation in children with hemoglobinopathies.

描述（申请人提供）：造血干细胞移植 造血干细胞移植（HSCT）已成为镰状细胞病患者的重要治疗选择 贫血或地中海贫血。虽然 HSCT 的来源通常是来自 HLA 相同的兄弟姐妹、脐带血 (CB) 可能被证明是重要的 资源。 CB可以含有足够数量的造血干细胞 清髓治疗后植入，无需完整的 HLA 即可使用 匹配，CB 诱发移植物抗宿主病 (GVHD) 的机会较小 比骨髓。为了增加用于这些目的的 CB 的可用性， 已开发了多家 CB 银行。然而，没有人关注兄弟姐妹 捐赠者脐带血（SDCB）采集，这个过程需要一套独特的 程序以适应在偏远地点进行收集，但没有一个程序具有广泛的 与有镰状细胞贫血症儿童的家庭合作的经验，或 地中海贫血。此修订后的应用程序包含两个具体目标：(1) 在目前有患有镰刀病的孩子的家庭中收集兄弟姐妹捐赠者的 CB 细胞性贫血或地中海贫血，以及 (2) 使用这些 CB 进行第一次 儿童CB移植的多中心前瞻性试点研究 这两种疾病。 CHORI 的 SDCB 计划将遵循以下程序： 符合脐带血库的标准。我们的可行性成功 研究表明我们的程序可以收集足够数量的 Cb 进行移植试验研究。有关的科学问题 移植失败、疾病复发、HLA 相容性以及 应用程序中解决了对关键数量的 HSC 的要求。 我们将检验一种新的免疫抑制调节的假设 治疗方案（氟达拉滨、环磷酰胺和白消安）和移植后 治疗（吗替麦考酚酯和环孢素）将改善植入 率并预防疾病复发。 SDCB移植的效果 将监测血液学参数和 GVHD。该试点的信息 研究将用于设计采用 SDCB 移植的新方法 血红蛋白病患者。总而言之，我们的最终目标是 建议将我们的 SDCB 计划的重点放在从家庭收集 CB 上 有一个患有血红蛋白病的孩子并使用这些 CB 来评估 CB 移植在这些儿童中的作用。我们预计我们的项目将 将SDCB移植领域从病例报告推进到临床 调查，将为进一步研究CB提供合理依据 患有血红蛋白病的儿童进行移植。