Background/Objectives: Despite the current international prognostic index for chronic lymphocytic leukemia (CLL) being widely accepted and broadly used, it does not consider the kinetics of the B-cell clone over time. Here, we investigated the potential association between distinct features of leukemic cells and other immune cells in blood and the kinetics of clonal B-cells in CLL stage Binet A/Rai 0 (A/0) patients; Methods: Based on the leukemia cell kinetics, 69 CLL A/0 cases followed for a median of 105 months were classified as carrying stable (n= 53) vs. rapidly increasing in size (n= 16) CLL clones; Results: Patients with increasing CLL clones had a significantly higher risk of disease progression and shortened time to first therapy vs. those carrying stable B-cell clones (p≤ 0.001). Strikingly, the distribution of various immune-cell populations in blood at diagnosis also differed significantly between the two groups, with lower Tαβ CD4+CD8locell counts (p= 0.03), a greater switched/unswitched memory B-cell ratio (p= 0.01), and higher plasma cell counts (p= 0.05) in CLL with increasing vs. stable clones. Multivariate analysis revealed that the number of circulating clonal B-cells (≥15 × 109/L) and Tαβ CD4+CD8locells (≤35 cells/µL), together with anIGHVunmutated gene status at diagnosis, were independent predictors of an increasing CLL clone; Conclusions: Altogether, these data suggest that the expansion of the CLL clone in stage A/0 patients may depend on both the intrinsic characteristics of CLL cells and the surrounding immune microenvironment.
背景/目的：尽管目前国际通用的慢性淋巴细胞白血病（CLL）预后指数被广泛接受和应用，但其未考虑B细胞克隆随时间变化的动力学特征。本研究旨在探讨Binet A/Rai 0分期（A/0期）CLL患者血液中白血病细胞与其他免疫细胞的特定特征与克隆性B细胞动力学之间的潜在关联。方法：根据白血病细胞动力学特征，对中位随访105个月的69例CLL A/0期患者进行分类，其中53例携带稳定克隆，16例携带快速扩增克隆。结果：与携带稳定B细胞克隆的患者相比，克隆扩增型CLL患者的疾病进展风险显著增高，首次治疗时间显著缩短（p≤0.001）。值得注意的是，两组患者诊断时血液中各免疫细胞亚群的分布也存在显著差异：与稳定克隆组相比，克隆扩增型CLL患者的Tαβ CD4+CD8lo细胞计数更低（p=0.03）、转换型/非转换型记忆B细胞比值更高（p=0.01）、浆细胞计数更高（p=0.05）。多变量分析显示，诊断时循环克隆性B细胞数量（≥15×10⁹/L）、Tαβ CD4+CD8lo细胞数量（≤35个/µL）以及IGHV未突变基因状态是克隆扩增型CLL的独立预测因子。结论：综合而言，这些数据表明A/0期患者CLL克隆的扩增可能同时取决于CLL细胞的内在特性和周围免疫微环境。
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