Background: Clinical staging (CS) and tumor burden (TB) play a significant role in FL prognosis and direct its up-front therapy. The aim of this study is to report prognostic factors and clinical outcomes in newly-diagnosed FL patients stratified according to CS and TB in early-stage (ES) disease, advanced-stage with low tumor burden (AS-LTB) and advanced-stage with high tumor burden (AS-HTB). Methods: Two hundred fourteen patients with FL grades 1-3A had baseline clinical characteristics and outcomes assessed. Survival according to up-front immunochemotherapeutic (ICT) regimens was assessed in the AS-HTB subgroup. Independent predictors for OS, PFS, POD-24, and Histological Transformation (HT) were identified. Results: Seventy-five percent of cases were categorized as AS-HTB, 13.5% as AS-LTB and 11.5% as ES. With a median follow-up of 8.15 years, the estimated 5-year OS and PFS were 75.4% and 57.2%, respectively. OS, but not PFS was markedly decreased in AS-HTB FL patients compared to ES and AS-LTB cases. POD-24 rate was 21.7% and overall mortality rate was 38.7% during the entire follow-up. The annual cumulative rate of HT to high-grade B-cell lymphoma (HGBCL) was 0.5%, and higher in AS-HTB cases, in comparison to ES and AS-LTB. Considering patients with AS-HTB there were no differences in clinical outcomes among cases submitted to ICT based on R-CHOP, R-CVP and regimens containing purine analogs. Additionally, ECOG ≥ 2, hypoalbuminemia, B-symptoms and HT were independently associated with poor survival. High content of centro-blasts (grade 3A), involvement of ≥3 nodal sites by FL and rituximab omission in up-front therapy predicted POD-24. Conclusions: FL has marked clinical-prognostic heterogeneity, translated into diverse CS and TB subcategories. Here, we demonstrated that FL patients classified as AS-HTB demonstrated decreased survival and higher rates of HT to HGBCL compared to ES and AS-LTB cases. Prognostic factors identified in our analysis may help to identify FL patients with higher-risk of HT and early-progression (POD-24).
Keywords: clinical outcomes; follicular lymphoma (FL); histological transformation (HT) to high-grade B-cell lymphoma (HGBCL); prognostic factors; progression of disease within 24 months from initial therapy (POD-24); staging; treatment modalities; tumor burden.