Abstract
BACKGROUND: Follicular lymphoma (FL) is an indolent yet highly heterogeneous B-cell lymphoproliferative disorder. The introduction of CD20 monoclonal antibodies has significantly improved patient survival; however, the optimal therapeutic strategy for grade 3A FL remains controversial. The Ki-67 proliferation index may reflect tumor aggressiveness, but its prognostic and therapeutic implications are not fully established. This study aimed to evaluate the prognostic significance of Ki-67 expression and to develop a predictive model for progression-free survival (PFS) in patients with grade 3A FL. METHODS: Clinical data from 110 patients with grade 3A FL were retrospectively analyzed. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors for PFS. Kaplan-Meier survival analysis with log-rank tests was used to compare PFS between subgroups stratified by Ki-67 expression and treatment regimen. A nomogram-based predictive model was constructed and validated using the concordance index (C-index), calibration plots, and decision curve analysis (DCA). RESULTS: High Ki-67 expression (≥ 50%) was associated with significantly shorter PFS. Among these patients, those treated with R-CHOP achieved longer PFS than those receiving BR, whereas the opposite trend was observed in patients with low Ki-67 expression (< 50%). High Ki-67 expression combined with CD5 positivity, CD10 negativity, or MUM1 positivity predicted poorer outcomes. Multivariate analysis identified Ki-67, stage, tumor diameter, B symptoms, and β(2)-microglobulin (β(2)-MG), as independent predictors of PFS. The constructed nomogram demonstrated good discrimination (C-index = 0.736) and superior predictive performance compared with FLIPI, FLIPI2, and PRIMA-PI. CONCLUSION: Grade 3A FL is characterized by marked clinical and biological heterogeneity. Our findings indicate that Ki-67 expression serves as a valuable prognostic marker that can inform therapeutic decision-making in patients with grade 3A FL. The proposed model integrating Ki-67 and clinical variables enhances PFS prediction and supports individualized treatment strategies for these patients.