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

Follicular lymphomas (FL) account for 25 to 30 % of non-Hodgkin's lymphomas. The course is mainly indolent but FL is a heterogeneous entity with both a risk of multiple relapses and a risk of transformation into a high-grade lymphoma with an especially poor prognosis. Evaluating these risks from the diagnosis helps to select the optimal treatment among the many available approaches. Clinical indices have been proposed for this purpose such as the Follicular Lymphoma International Prognostic Index 1 (FLIPI 1) for overall survival and the FLIPI 2 for progression-free survival. The discriminatory capacity of the FLIPI 1 has been confirmed by several retrospective and prospective studies, while these analyses are ongoing for the FLIPI 2. However, these clinical indices cannot account for all of the heterogeneity of the course of FL, and numerous biological studies of prognostic parameters have been undertaken. Gene profile studies have shown that the prognosis of FL was not related to the signature of FL cells, but to the signature of various cells of the microenvironment such as macrophages, T cells, and follicular dendritic cells. Most of the immunohistochemical studies of the microenvironment have yielded discrepant results, and have not allowed a simple and accurate biological prognostic index to be proposed that could be used in routine clinical practice. The interactive relationships between FL cells and the microenvironment remain to be clarified. The studies required for this are all the more difficult to perform since treatments have a great influence on these relationships.