Radioimmunotherapy-based conditioning regimens for stem cell transplantation

Radioimmunotherapy (RIT) combines the mechanism of action and targeting capability of monoclonal antibodies with the tumoricidal effect of radiation and has shown promising results in the treatment of various hematologic malignancies. Based on RIT's efficacy and safety profile, many investigators have evaluated its use in transplant conditioning regimens with the goal of improving long-term disease control with limited toxicity. In lymphoma, two basic transplant approaches targeting CD20 have emerged: (1) myeloablative doses of RIT with or without chemotherapy, and (2) standard nonmyeloablative doses of RIT combined with high-dose chemotherapy. Myeloablative RIT has been shown to be feasible and efficacious using escalated doses of iodine 131-tositumomab, yttrium 90-ibritumomab tiuxetan, and (131)I-rituximab with or without chemotherapy followed by autologous stem cell transplant (ASCT). The second approach predominantly has used standard doses of (90)Y-ibritumomab tiuxetan or (131)I-tositumomab plus BEAM chemotherapy (carmustine [BCNU], etoposide, cytarabine, melphalan) followed by ASCT. RIT targeting CD45, CD33, and CD66 prior to allogeneic transplantation also has been evaluated for the treatment of acute leukemia. Overall RIT-based transplant conditioning for lymphoma and leukemia has been shown to be safe, effective, and feasible with ongoing randomized trials currently underway to definitively establish its place in the treatment of hematologic malignancies.