Radioimmunotherapeutic strategies in autologous hematopoietic stem-cell transplantation for malignant lymphoma

High-dose therapy followed by autologous hematopoietic stem-cell transplantation is the preferred therapy for relapsed chemotherapy-sensitive aggressive non-Hodgkin lymphoma, and may play a role in the treatment of high-risk first-remission aggressive lymphomas, mantle-cell lymphomas and relapsed follicular lymphomas. The primary cause of failure of this approach is disease recurrence despite initial responses. Traditional high-dose regimens have relied upon myeloablative combinations of chemotherapy with or without total body irradiation. In the Western world, over 90% of lymphomas are of B-cell origin, and the vast majority of those that come to transplant remain CD20-positive. The development of radioimmunotherapeutic approaches targeting this antigen allows for either dose escalation with stem-cell support, or the addition of targeted therapy to conditioning regimens either as a replacement for total body irradiation or in addition to myeloablative chemotherapy regimens. Results to date with yttrium-90 ibritumomab tiuxetan (Zevalin®) and I-131 tositumomab (Bexxar®) suggest that the addition of radioimmunoconjugate therapy to conventional conditioning regimens results in a toxicity profile similar to that seen with chemotherapy conditioning alone. Demonstration of improved disease control will ultimately require phase-III studies, though preliminary results are promising.