Risk prediction for clonal cytopenia: multicenter real-world evidence.

IF 21 1区 医学 Q1 HEMATOLOGY
Blood Pub Date : 2024-11-07 DOI:10.1182/blood.2024024756
Zhuoer Xie, Rami Komrokji, Najla Al Ali, Alexandra Regelson, Susan Geyer, Anand Patel, Caner Saygin, Amer M Zeidan, Jan Philipp Bewersdorf, Lourdes Mendez, Ashwin Kishtagari, Joshua F Zeidner, Catherine C Coombs, Yazan F Madanat, Stephen Chung, Talha Badar, James Foran, Pinkal Desai, Charlton Tsai, Elizabeth A Griffiths, Monzr M Al Malki, Idoroenyi Amanam, Catherine Lai, H Joachim Deeg, Lionel Ades, Cecilia Arana Yi, Afaf E G Osman, Shira Dinner, Yasmin Abaza, Justin Taylor, Namrata Chandhok, Deborah Soong, Andrew M Brunner, Hetty E Carraway, Abhay Singh, Chiara Elena, Jacqueline Ferrari, Anna Gallì, Sara Pozzi, Eric Padron, Mrinal M Patnaik, Luca Malcovati, Michael R Savona, Aref Al-Kali
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引用次数: 0

Abstract

Abstract: 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 patients with CCUS 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 of <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 of <2.5 points), intermediate- (score of 2.5 to <5), and high-risk (score of ≥5) groups. The CCRS effectively predicted 2-year cumulative incidence of MN for low- (6.4%), intermediate- (14.1%), and high-risk (37.2%) groups, respectively, by the Gray 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.

克隆性细胞减少症的风险预测:多中心真实世界证据
意义未定的克隆性细胞减少症(CCUS)是一种独特的疾病实体,其特点是在有不明原因的细胞减少症但没有髓系肿瘤(MN)的个体中,存在髓系相关的体细胞突变,其变异等位基因比例≥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需要进行专门研究,以阐明其风险因素和自然病史。我们对 357 例 CCUS 患者进行了分析,研究了克隆性、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(得分 = 2 分)、血小板计数(得分 = 1 分)、细胞减少(得分 = 1 分)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Blood
Blood 医学-血液学
CiteScore
23.60
自引率
3.90%
发文量
955
审稿时长
1 months
期刊介绍: Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.
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