意义未明的克隆性血细胞减少症 (CCUS) 是一种独特的疾病实体，其特征是骨髓相关体细胞突变，在患有不明原因血细胞减少但无骨髓肿瘤 (MN) 的个体中，变异等位基因比例≥2%。值得注意的是，CCUS 有进展为 MN 的风险，特别是在具有高风险突变的病例中。了解 CCUS 需要专门的研究来阐明其风险因素和自然史。我们对 357 名 CCUS 患者进行分析，调查了克隆性、血细胞减少和预后之间的相互作用。多变量分析确定了3个关键的不良预后因素：存在剪接突变（评分= 2分）、血小板计数<100×109/L（评分= 2.5）和≥2个突变（评分= 3）。变量分数基于 Cox 比例风险模型的系数。这导致了克隆性血细胞减少风险评分 (CCRS) 的发展，它将患者分为低风险（评分 <2.5 分）、中风险（评分 2.5-<5）和高风险（评分≥5）组。通过格雷检验，CCRS 分别有效预测了低风险组 (6.4%)、中风险组 (14.1%) 和高风险组 (37.2%) 的 MN 2 年累积发病率 (P <.0001)。我们通过将 CCRS 应用于 104 名患者的独立 CCUS 队列进一步验证了 CCRS，证明在对 MN 累积发病率进行分层时 c 指数为 0.64 (P =.005)。我们的研究强调了整合临床和分子数据来评估 CCUS 进展风险的重要性，使 CCRS 成为实用且易于计算的宝贵工具。这些发现具有临床意义，可制定 CCUS 管理策略并为未来的临床试验设计提供信息。版权所有 © 2024 美国血液学会。

Clonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history. Our analysis of 357 CCUS patients investigated the interplay between clonality, cytopenia, and prognosis. Multivariate analysis identified 3 key adverse prognostic factors: the presence of splicing mutation(s) (score = 2 points), platelet count <100×109/L (score = 2.5), and ≥2 mutations (score = 3). Variable scores were based on the coefficients from the Cox proportional hazards model. This led to the development of the Clonal Cytopenia Risk Score (CCRS), which stratified patients into low- (score <2.5 points), intermediate- (score 2.5-<5), and high-risk (score ≥5) groups. The CCRS effectively predicted 2-year cumulative incidence of MN for low- (6.4%), intermediate- (14.1%), and high- (37.2%) risk groups, respectively, by Gray's test (P <.0001). We further validated the CCRS by applying it to an independent CCUS cohort of 104 patients, demonstrating a c-index of 0.64 (P =.005) in stratifying the cumulative incidence of MN. Our study underscores the importance of integrating clinical and molecular data to assess the risk of CCUS progression, making the CCRS a valuable tool that is practical and easily calculable. These findings are clinically relevant, shaping the management strategies for CCUS and informing future clinical trial designs.Copyright © 2024 American Society of Hematology.