Front-line therapy for nonlocalized diffuse large B-cell lymphoma: what has been demonstrated and what is yet to be established

The field of treatment of diffuse large B-cell lymphoma has been in a continuous flux over the last 10-15 years owing to the introduction of new therapeutic approaches such as dose-dense chemotherapy, monoclonal antibodies and high-dose chemotherapy followed by autologous peripheral blood stem cell transplant. The use of clinical prognostic factors has improved our ability to predict the outcome of these lymphomas; moreover, the gene and protein expression pattern has been shown, at least in the pre-rituximab era, to be an independent and powerful prognostic indicator. This review will focus on results obtained in the last decade by large clinical trials evaluating the first-line therapy in nonlocalized diffuse large B-cell lymphoma; special emphasis will be placed on more mature results that can be indicated as 'standard' therapy. Ongoing studies addressing as yet unanswered or controversial questions will be analyzed, and preliminary data will be critically reviewed.