Sibling Donor Cord Blood Banking and Transplantation

描述(申请人提供)：造血干细胞移植 (HSCT)已成为镰状细胞患者的重要治疗选择 贫血或地中海贫血。而HSCT的来源通常是来自 人类白细胞抗原完全相同的兄弟姐妹，脐带血(CB)可能被证明是一个重要的 资源。脐带血可以含有足够数量的造血干细胞 清髓治疗后植入，不需要完整的人类白细胞抗原即可使用 匹配，CB诱发移植物抗宿主病(GVHD)的机会较小 而不是骨髓。为了增加用于这些目的的炭黑的可用性，一个 多家可转债银行已经发展起来。然而，没有一个人关注兄弟姐妹 捐献者脐带血(SDCB)采集，这一过程需要一套独特的 程序，以适应远程站点的收集，并且没有一个具有广泛的 与孩子患有镰状细胞性贫血或 地中海贫血。修订后的申请书包含两个具体目标：(1) 在目前有镰刀孩子的家庭中收集兄弟姐妹捐赠者CB 细胞性贫血或地中海贫血以及(2)使用这些CBS进行第一次 儿童脐带血移植多中心前瞻性先导性研究 这两种疾病。CHORI的SDCB计划将遵循以下程序 遵守脐带血库的标准。我们成功的可行性 研究表明，我们的程序可以收集足够数量的CBS 进行中试移植研究。关于以下的科学问题 移植失败、疾病复发、人类白细胞抗原相容以及 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条件作用的假设 方案(氟达拉滨、环磷酰胺和丁硫丹)和移植后 治疗(霉酚酸酯和环孢菌素)将提高植入率 降低发病率，防止疾病复发。自体脐带血移植对大鼠心脏功能的影响 血液学参数和GVHD将被监测。有关此试点项目的信息 研究将用于设计使用自体脐血移植的新方法 患有血红蛋白疾病的患者。总而言之，我们的最终目标是 建议是将我们的SDCB计划的重点放在从家庭中收集CBS 有一个患有血红蛋白病的孩子，并使用这些CBS评估 脐带血移植在这些儿童中的作用。我们预计我们的项目将 将自体脐血移植领域从病例报道推向临床 为进一步研究CB提供了合理的依据 患有血红蛋白疾病的儿童的移植。

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.