The role of stem-cell transplantation in the treatment of marginal zone lymphoma.

High-dose chemotherapy and autologous stem-cell transplantation (ASCT) is standard therapy in relapsed/refractory aggressive lymphoma. The optimal therapy of relapsed/refractory disseminated marginal-zone lymphoma (MZL) has not been defined. Limited data on ASCT in this setting suggests outcomes are similar to what is expected in follicular lymphoma. International guidelines suggest that ASCT should be considered in follicular lymphoma in second or subsequent remission, in particular in high-risk disease, or following disease transformation. These guidelines can be extrapolated to MZL. ASCT is not considered curative but a subset of patients achieve very long remissions. The major concern is the occurrence of secondary malignancies possibly related to total-body irradiation. Allogeneic SCT is usually considered after failure of ASCT, but can also be considered upfront in younger patients seeking curative approach. The introduction of novel/targeted therapies may change the role and timing SCT may have in the treatment algorithm of indolent lymphomas.

Radioimmunotherapy and Autologous Stem-Cell Transplantation in the Treatment of B-Cell Non-Hodgkin Lymphoma.

High-dose chemotherapy and autologous stem-cell transplantation (ASCT) is the standard therapy for patients with chemosensitive-relapsed or chemosensitive-refractory aggressive lymphoma. The use of rituximab, an anti-CD20 monoclonal antibody, has dramatically changed the outcome of patients with aggressive lymphoma, increasing both response and survival rates. However, despite this progress a significant proportion of patients are still refractory or relapse after frontline rituximab-containing therapy. Moreover, it is increasingly more difficult to rescue these patients with current salvage chemotherapy and ASCT approaches. Novel approaches are needed for these high-risk patients, especially in the rituximab era. Radioimmunotherapy (RIT) is a form of targeted therapy using the parent monoclonal antibody to deliver radiation emitted by a conjugated radioisotope, to the vicinity of antigen-positive tissues. Two radioimmunoconjugates--yttrium-90 ibritumomab tiuxetan (Zevalin) and iodine-131 tositumomab (Bexxar) have been in clinical use. There are multiple studies demonstrating the safety and efficacy of both agents in both indolent and aggressive lymphoma. Radiolabeled antibodies are ideal candidates to combine with high-dose chemotherapy and ASCT. RIT targets radiation to disease sites while limiting exposure of uninvolved critical organs, thus it can safely replace total-body irradiation during conditioning for ASCT. The major toxicity and limiting factor in RIT is myelotoxicity that is easily reversed by stem-cell rescue. RIT can be combined at standard doses with high-dose chemotherapy or can be given in escalated doses either alone or with high-dose chemotherapy before ASCT. Several phase II studies have shown the safety and potential efficacy of both agents using these approaches. A small randomized study comparing standard-dose Zevalin with combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) high-dose chemotherapy and BEAM alone suggested a survival advantage of Zevalin-BEAM. However, a large randomized study comparing Bexxar-BEAM and rituximab-BEAM did not show any advantage. More studies are needed to establish the role and the dose of RIT given for ASCT.

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

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.