Sibling Donor Cord Blood Banking and Transplantation

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的来源通常是骨髓， 一个HLA相同的同胞，脐带血（CB）可能被证明是一个重要的 resource. CB可以含有足够数量的造血干细胞， 清髓性治疗后的移植，可以在没有完整HLA的情况下使用 CB与GVHD完全匹配，并且CB诱导移植物抗宿主病（GVHD）的机会较小。 而不是骨髓。为了增加CB在这些方面的可用性， 已经开发了许多CB银行。然而，没有人关注兄弟姐妹 供体脐带血（SDCB）采集，这一过程需要一套独特的 程序，以适应收集在远程站点，没有广泛的 有与患有镰状细胞性贫血的孩子的家庭合作的经验， 地中海贫血这一修订的申请包含两个具体目标：（1） 在目前有一个患有镰刀病的孩子的家庭中收集同胞供体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 CB移植在儿童中的多中心前瞻性初步研究 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。我们的可行性的成功 研究表明，我们的程序可以收集足够数量的CBS 进行初步移植研究。科学问题， 移植失败，疾病复发，HLA相容性，以及 在本申请中解决了对HSC临界数量的要求。 我们将检验一种新的免疫抑制条件反射 方案（氟达拉滨、环磷酰胺和白消安）和移植后 治疗（霉酚酸酯和环孢素）将改善植入 预防和预防疾病复发。SDCB移植后对小鼠脾细胞增殖的影响 将监测血液学参数和GVHD。此试点的信息 研究将用于设计采用SDCB移植的新方法， 血红蛋白病患者。总之，我们的最终目标是 我们的建议是将SDCB计划的重点放在从家庭收集CB上 有一个孩子患有血红蛋白病，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 为进一步研究CB提供了合理的依据 在患有血红蛋白病的儿童中进行移植。

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.