Radiolabeled antibodies directed at CD45 for conditioning prior to allogeneic transplantation in acute myeloid leukemia and myelodysplastic syndrome

Abstract

While allogeneic hematopoietic cell transplantation (HCT) may offer the best chance of cure for patients suffering from aggressive hematological malignancies such as acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome, successful outcomes for the subgroup of patients with high-risk disease remain disappointing and lag behind those of lower-risk patients. Because relatively high rates of relapse are an important contributor to these poor outcomes, efforts have explored approaches to increase the cytotoxic effects of treatment. Relapse rates have been shown to improve with the addition of increased doses of total body irradiation (TBI) and/or the introduction of additional chemotherapy to a HCT conditioning regimen. However, the increase in TBI dose and/or additional chemotherapy has also been associated with a significant increase in life-threatening toxicities, resulting in no change in overall survival. Radioimmunotherapy (RIT) has been employed as an adjunct to HCT where targeted delivery of radiation may allow for further escalation of therapy to reduce relapse with minimal toxicity. In this review we describe these efforts, including the benefits of escalating the dose of radiation to sites of hematologic disease prior to HCT, the various cellular targets for antibody-mediated delivery of radiation, as well as the rationale for incorporation of various radionuclides such as alpha emitters and beta emitters into the preparative regimen prior to HCT. Lastly, newer novel approaches such as pretargeted RIT (PRIT) are described as a method to further increase delivery of targeted radiation to hematological tissues while sparing noninvolved organs.