RADIOLABELED BC8, FLUDARABINE, TBI FOLLOWED BY PBSC TRANSPLANT FOR ADVANCED AML

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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.