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Background <p>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.</p> Methods <p>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).</p> Results <p>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 (&lt; 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<sub>2</sub>-microglobulin (β<sub>2</sub>-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.</p> Conclusion <p>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.</p>

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Prognostic significance of Ki-67 in grade 3A follicular lymphoma and development of a novel PFS nomogram

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月16日

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  • Xinyue Li,
  • Qi Zhao,
  • Ling Li,
  • Lei Zhang,
  • Xinhua Wang,
  • Xiaorui Fu,
  • Zhenchang Sun,
  • Zhaoming Li,
  • Yu Chang,
  • Cunzhen Shi,
  • Xiaolong Wu,
  • Chenlin Zhao,
  • Yilin Zhang,
  • Mingzhi Zhang,
  • Xin Li

摘要

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 β2-microglobulin (β2-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.