Splenic marginal zone lymphoma with and without villous lymphocytes

Splenic marginal zone lymphoma with or without villous lymphocytes (SLVL/SMZL) is a low grade B-cell lymphoma that affects patients in the sixth decade and has a median survival greater than 10 years. A substantial proportion of patients die from causes unrelated to the disease. Close to a third of the patients do not require intervention and a policy of watch and see is reasonable and recommended. There are several therapeutic options that have proved effective in these patients. Due to the natural history of the lymphoma, the main goal of all these treatments is to achieve control of the disease rather than its eradication. Retrospective designs of all documented studies, the lack of uniform response criteria and the heterogeneity in the patient's features makes interpretation of the data difficult. Splenectomy remains one of the first line options in patients fit for surgery. Amongst chemotherapy, purine analogues, in particular fludarabine in combination or not with Rituximab and Rituximab alone have a greater efficacy than alkylating agents in terms of achieving better quality of response and longer progression free survival; therefore these agents are recommended particularly in patients who are not candidates for surgery or relapse after splenectomy. In the small proportion of patients with concomitant hepatitis C virus (HCV) infection, Interferon-alpha, ribavirin or a combination of both has demonstrated a significant activity with responses correlating with clearance of HCV RNA in the blood; therefore, these agents should be considered in the therapeutic scenario as a first line in these small cohort of patients. Patients that transform to high-grade lymphoma and the minority that have TP53 abnormalities should be treated with other schedules. Prospective randomized trials would be desirable to ascertain the independent prognostic factors and the biological features that predict disease progression and drug resistance to device the optimal management and treatment for SLVL/SMZL.