Radioimmunotherapy and stem-cell transplantation in the treatment of aggressive B-cell lymphoma

Abstract

High-dose chemotherapy and autologous stem-cell transplantation (ASCT) have an established therapeutic role in the treatment of chemo-sensitive relapsed aggressive lymphoma, but has limited success in chemo-refractory disease or in heavily pretreated, multiple relapsed patients. Recurrent disease is the major cause of treatment failure in all patient subsets and the majority is not cured. Methods for better eradication of underlying lymphoma are needed to improve outcome. Radioimmunotherapy (RIT) combines radiation delivered by radio-isotopes with the targeting effect of monoclonal antibodies. Two radioimmunoconjugates are currently approved for relapsed/resistant low-grade or transformed lymphoma: iodine-131 tositumomab and yttrium-90 ibritumomab tiuxetan. These agents are also effective in aggressive lymphoma. Radio-labeled antibodies are ideal candidates to combine with high-dose chemotherapy and ASCT. Their major toxicity is myelosuppression, which is easily reversed by ASCT and they can target disease sites with almost no added toxicity to normal tissues. RIT has been used in escalated doses as the sole treatment prior to ASCT or in standard or escalated doses combined with standard high-dose chemotherapy regimens. RIT was also combined with reduced-intensity conditioning and allogeneic SCT. Preliminary results are promising and suggest improved disease control with no added toxicity; however randomized studies are needed to confirm these initial observations.