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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。尽管20多年来骨髓移植取得了许多进步，但晚期AML移植患者的无白血病存活率仍然相对较低。我们已经进行了使用放射性碘(131I标记的BC8[抗CD45])抗体将定向造血照射输送到骨髓、脾和淋巴结的研究，以努力在不增加移植相关死亡率的情况下提高白血病细胞的杀伤率和减少复发。这种方法使我们能够向骨髓和脾发射比向肝脏(正常器官通常接受最高辐射剂量)多两到三倍的辐射。这项试验将131I-BC8抗体递增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(超过首次缓解、原发难治性疾病或由MDS/MPS演变而来)或高危MDS的老年患者(50岁及以上)的疾病控制，同时不大幅增加移植方案的毒性。具体地说，这项研究将确定131I-BC8抗体联合非清髓方案氟达拉滨和2Gy全身照射(TBI)，加上CSP/MMF，然后进行相关或非相关异基因HSCT的最大耐受剂量。这项研究还将评估联合制备方案导致的供者嵌合体水平，以及与抗体传递到造血组织的辐射剂量以及缓解效果和持续时间的相关性。

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.