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 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。尽管二十多年来骨髓移植取得了许多进步，但因晚期 AML 移植的患者的无白血病生存率仍然相对较差。我们进行了研究，使用放射性碘（131I标记的BC8 [抗CD45]）抗体对骨髓、脾脏和淋巴结进行靶向造血照射，以提高白血病细胞杀伤率并减少复发，同时避免过高的移植相关死亡率。这种方法使我们能够向骨髓和脾脏输送比肝脏（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 131I-BC8 抗体逐渐增加剂量的靶向造血放射与非清髓性移植相结合，旨在改善患有晚期 AML（超出首次缓解、原发性难治性疾病或进化而来）的老年患者（50 岁及以上）的疾病控制。 MDS/MPS）或高风险MDS，而不会显着增加移植方案的毒性。具体来说，本研究将确定通过 131I-BC8 抗体结合氟达拉滨非清髓治疗方案和 2 Gy 全身照射 (TBI)，加上 CSP/MMF，然后进行相关或不相关的同种异体 HSCT 的最大耐受辐射剂量。该研究还将评估联合准备方案产生的供体嵌合水平，以及与抗体递送至造血组织的辐射剂量的相关性以及缓解的成就和持续时间。