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
{"title":"Risk prediction for clonal cytopenia: multicenter real-world evidence.","authors":"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","doi":"10.1182/blood.2024024756","DOIUrl":null,"url":null,"abstract":"<p><strong>Abstract: </strong>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.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2033-2044"},"PeriodicalIF":21.0000,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561536/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1182/blood.2024024756","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
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.
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.