Biologic predictors in follicular lymphoma: Importance of markers of immune response

We sought to identify biologic indicators of prognosis in a series of 94 follicular lymphoma (FL) patients, focusing on markers of the host immune response as well as of B-cell maturation. Immune response was assessed with immunostains for CD68 (for lymphoma-associated macrophages, LAMs) and FOXP3 (regulatory T-cells). Lymphoma cells were evaluated for expression of bcl-2, CD10, and MUM-1. Clinical data were obtained for FLIPI, presence of bulky disease, presence of B-symptoms, treatment, and overall survival (OS). For the 69 initially treated patients, extrafollicular CD68+ cells (ef-CD68) and follicular FOXP3+ cells (f-FOXP3) were associated with shorter OS, while receipt of rituximab was associated with longer OS. Multivariable analysis showed ef-CD68 was the only independent factor associated with shorter OS. In subset analysis, ef-CD68 remained statistically significant in rituximab-naive but not rituximab-treated patients. We confirm the importance of LAMs and f-FOXP3 as predictors of OS in FL.