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).
背景：临床分期（CS）与肿瘤负荷（TB）在滤泡性淋巴瘤（FL）的预后判断及初始治疗方案选择中具有重要作用。本研究旨在根据CS和TB将初诊FL患者分为早期（ES）、低肿瘤负荷晚期（AS-LTB）及高肿瘤负荷晚期（AS-HTB）三类，并报告其预后因素与临床结局。 方法：对214例1-3A级FL患者的基线临床特征及结局进行评估。在AS-HTB亚组中，评估了不同初始免疫化疗（ICT）方案对生存的影响。确定了总生存期（OS）、无进展生存期（PFS）、24个月内疾病进展（POD-24）和组织学转化（HT）的独立预测因素。 结果：75%的病例被归类为AS-HTB，13.5%为AS-LTB，11.5%为ES。中位随访8.15年，预估5年OS和PFS分别为75.4%和57.2%。与ES和AS-LTB病例相比，AS-HTB FL患者的OS（而非PFS）显著降低。整个随访期间，POD-24发生率为21.7%，总死亡率为38.7%。转化为高级别B细胞淋巴瘤（HGBCL）的年累积发生率为0.5%，且AS-HTB病例的发生率高于ES和AS-LTB病例。在AS-HTB患者中，接受基于R-CHOP、R-CVP及含嘌呤类似物方案的ICT治疗的患者，其临床结局无显著差异。此外，ECOG评分≥2分、低白蛋白血症、B症状和HT与不良生存独立相关。中心母细胞高含量（3A级）、FL累及≥3个淋巴结区域以及初始治疗中未使用利妥昔单抗是POD-24的预测因素。 结论：FL具有显著的临床-预后异质性，这体现在不同的CS和TB亚类中。本研究证实，与ES和AS-LTB病例相比，归类为AS-HTB的FL患者生存期缩短，且转化为HGBCL的发生率更高。我们分析中确定的预后因素可能有助于识别HT和早期进展（POD-24）风险较高的FL患者。
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