RADIOLABELED BC8, FLU, TBI AND PBSC TRANSPLANT FOR ELDERLY AML OR MDS PATIENTS

为老年 AML 或 MDS 患者进行放射性标记 BC8、FLU、TBI 和 PBSC 移植

• 批准号: 7379339
• 负责人: JOHN M PAGEL
• 金额: $ 0.17万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7379339
• 关键词: RADIOLABELED; BC8; FLU; TBI; PBSC

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Despite many improvements in bone marrow transplantation over more than two decades, the leukemia-free survival for patients transplanted for advanced AML remains relatively poor. We have conducted studies using radioactive iodine (131I-labeled BC8 [anti-CD45]) antibody to deliver targeted hematopoietic irradiation to marrow, spleen and lymph nodes in an effort to improve leukemia cell kill and decrease relapse without excessive transplant-related mortality. This method has allowed us to deliver as much as two to three times more radiation to the bone marrow and spleen than to the liver (the normal organ typically receiving the highest radiation dose). This trial combines escalating doses of targeted hematopoietic radiation delivered by 131I-BC8 antibody with non-myeloablative transplantation in an effort to improve disease control for elderly patients (age 50 and above) with advanced AML (beyond first remission, primary refractory disease, or evolved from MDS/MPS) or with high risk MDS, without substantially increasing the toxicity of the transplant regimen. Specifically, this study will determine the maximally tolerated dose of radiation delivered via 131I-BC8 antibody combined with the non-myeloablative regimen of fludarabine and 2 Gy total body irradiation (TBI), plus CSP/MMF, followed by related or unrelated allogeneic HSCT. The study will also evaluate level of donor chimerism resulting from the combined preparative regimen, and correlation with radiation doses delivered to hematopoietic tissues by antibody as well as achievement and duration of remission.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。尽管在过去的二十多年里，骨髓移植取得了许多进展，但晚期AML移植患者的无白血病生存率仍然相对较低。我们进行了使用放射性碘（131 I标记的BC 8 [抗CD 45]）抗体对骨髓、脾脏和淋巴结进行靶向造血照射的研究，以提高白血病细胞杀伤率并减少复发，而不会导致过度的移植相关死亡率。这种方法使我们能够向骨髓和脾脏提供比肝脏（通常接受最高辐射剂量的正常器官）多两到三倍的辐射。该试验将由131 I-BC 8抗体递送的靶向造血放射的递增剂量与非清髓性移植相结合，以努力改善患有晚期AML（超过首次缓解、原发性难治性疾病或从MDS/MPS演变而来）或患有高风险MDS的老年患者（50岁及以上）的疾病控制，而基本上不增加移植方案的毒性。具体而言，本研究将确定通过131 I-BC 8抗体联合氟达拉滨和2戈伊全身照射（TBI）的非清髓方案，加上CSP/MMF，随后进行相关或不相关的同种异体HSCT递送的最大耐受剂量。本研究还将评价联合制备方案产生的供体嵌合体水平，以及与通过抗体递送至造血组织的辐射剂量的相关性，以及缓解的实现和持续时间。