Follicular lymphoma prognostic factors in the modern era: what is clinically meaningful?

Follicular lymphomas (FL) account for 30% of non-Hodgkin's lymphomas (NHL). Their evolution is heterogeneous. Some patients present with indolent forms undergoing several relapses while in other patients the disease evolves abruptly toward aggressive NHL. This is why accurate prognostic indices are required so that treatment strategies may be optimized for each patient and so that trials may be conducted in groups of patients that are as homogeneous as possible. The Follicular Lymphoma International Prognostic Index (FLIPI) has been designed to separate patients into 3 groups with significantly different hazard ratios for death. Its accuracy has been confirmed in several studies. The FLIPI2 was designed more recently to separate patients with significantly different hazard ratios for progression/relapse in the era of anti-CD20 monoclonal antibody treatments. Gene profile studies have shown that the prognosis of FL is mainly related to the type, number, and activation of immune cells in the microenvironment of lymphomatous follicles. Immunohistochemical studies suggest that macrophages, CD4+ T cells and among them T-regulatory cells (T-regs) and programed death-1 cells (PD-1 cells) play a major role in the outcome of FLs. However, additional confirmatory studies are required due to discrepancies in results. Up to now, these biological study results are more useful for approaching the pathophysiology of FL rather than to be used as prognostic tools in clinical practice.