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: 7603447
• 负责人: JOHN M PAGEL
• 金额: $ 0.11万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603447
• 关键词: Achievement; Age; Allogenic; Antibodies; Bone Marrow; Bone Marrow Transplantation; Chimerism; Computer Retrieval of Information on Scientific Projects Database; Disease remission; Dose; Elderly; Funding; Grant; Hematopoietic; Institution; Label; Liver; Marrow; Maximum Tolerated Dose; Methods; Organ; Patients; Peripheral Blood Stem Cell; Radiation; Radioactive Iodine; Refractory Disease; Relapse; Research; Research Personnel; Resources; Risk; Source; Spleen; Time; Toxic effect; Transplant Recipients; Transplantation; Treatment Protocols; United States National Institutes of Health; Whole-Body Irradiation; cell killing; disorder control; fludarabine; hematopoietic tissue; improved; irradiation; leukemia; lymph nodes; mortality; older patient

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 尽管在超过二十年中，骨髓移植的改善了，但用于晚期AML移植的患者的无白血病生存率仍然相对较差。 我们已经使用放射性碘（131i标记的BC8 [抗CD45]）抗体进行了研究，以将靶向的造血辐射传递给骨髓，脾和淋巴结，以改善白血病细胞杀死和降低复发的杀死，而无需过多的复发。 这种方法使我们能够向骨髓和脾脏传递多达两到三倍的辐射，而不是肝脏（正常器官通常接受最高辐射剂量）。 该试验结合了131I-BC8抗体和非肌能移植的靶向造血辐射的不断升级剂量，以改善患有晚期AML的老年患者（50岁及以上）患有晚期AML的疾病控制（超过第一次缓解，主要的折磨性疾病，初级验力疾病，或从MDS/MPS/MDS中产生的高风险MDS或高风险MDS的毒性增加，而不是有害的MDS造成强大的毒性。 具体而言，这项研究将确定通过131I-BC8抗体递送的最大耐受剂量以及氟达拉滨和2 GY总体辐照（TBI）的非毛囊治疗方案，加上CSP/MMF，随后是相关或不相关的同种异体HSCT。 该研究还将评估由组合方案的组合方案产生的供体嵌合体水平，并与通过抗体以及成就和缓解持续时间递送到造血组织的辐射剂量相关。