Chronic systemic inflammation is a key driver of polycythemia vera (PV) progression, but the immunomodulatory effects of current treatments remain poorly defined. The neutrophil-to-lymphocyte ratio (NLR) is an accessible biomarker of systemic inflammation proven in other contexts, but its role in monitoring PV disease activity has not been established. Using data from three of the largest PV clinical trials, we evaluated the effects of PV therapies on NLR and its relationship with molecular response and clinical outcomes. In 404 hematocrit-controlled patients from the ECLAP study, hydroxyurea (HU) failed to significantly lower NLR (p = 0.11) due to the parallel declines in ANC and ALC. Neither leukocyte counts nor NLR were significantly reduced by phlebotomy in ECLAP patients treated without cytoreductive therapy. In contrast, the Low-PV study showed that while phlebotomy tended to increase NLR, low-dose ropeginterferon alfa-2b (Ropeg) significantly reduced NLR (−18.2% and −36.3% in patients with low and high baseline NLR, respectively) by suppressing ANC rather than lymphocytes. NLR reduction correlated with the primary Low-PV endpoint (p = 0.021) and reduction of JAK2 variant allele frequency (VAF) [1]. The PROUD-PV/CONTINUATION-PV study confirmed the superior effect of Ropeg over HU, with a significantly greater NLR reduction at 60 months (−56.5% versus −33.6%, respectively, p = 0.019) in patients with high baseline NLR. Moreover, NLR reduction was associated with decreased JAK2V617F VAF (p < 0.0001) and improved event-free survival (p = 0.010). These findings identify NLR as a dynamic biomarker of treatment response and prognosis in PV and support its incorporation into routine monitoring.
慢性系统性炎症是真性红细胞增多症（PV）进展的关键驱动因素，但现有治疗的免疫调节效应仍未明确。中性粒细胞与淋巴细胞比值（NLR）作为系统性炎症的易获取生物标志物已在其他疾病中得到验证，但其在PV疾病活动监测中的作用尚未确立。通过分析三项最大规模PV临床试验的数据，我们评估了PV治疗对NLR的影响及其与分子应答和临床结局的关系。在ECLAP研究的404例血细胞比容控制患者中，羟基脲（HU）因中性粒细胞计数（ANC）和淋巴细胞计数（ALC）同步下降而未能显著降低NLR（p=0.11）。在未接受细胞减灭治疗的ECLAP患者中，放血疗法既未显著降低白细胞计数也未降低NLR。相比之下，Low-PV研究表明，放血疗法有升高NLR的趋势，而低剂量罗培干扰素α-2b（Ropeg）通过抑制ANC而非淋巴细胞，使基线NLR低值和高值患者的NLR分别显著降低18.2%和36.3%。NLR降低与Low-PV主要终点相关（p=0.021），且与JAK2变异等位基因频率（VAF）下降有关[1]。PROUD-PV/CONTINUATION-PV研究证实了Ropeg优于HU，在基线高NLR患者中60个月时NLR降幅显著更大（分别为-56.5% vs -33.6%，p=0.019）。此外，NLR降低与JAK2V617F VAF下降（p<0.0001）和无事件生存期改善（p=0.010）相关。这些发现确立了NLR作为PV治疗反应和预后的动态生物标志物，支持将其纳入常规监测体系。
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