The Clinical Challenge of Idiopathic Cytopenias of Undetermined Significance (ICUS) and Clonal Cytopenias of Undetermined Significance (CCUS)

  • David P. SteensmaEmail author
Myelodysplastic Syndromes (M Savona, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Myelodysplastic Syndromes


Purpose of Review

To review terminology, diagnostic algorithms, and clinical outcomes for patients with unexplained blood cytopenias.

Recent Findings

Patients with cytopenias that remain unexplained after organized diagnostic testing can be described as having “idiopathic cytopenias of undetermined significance” (ICUS). Patients with unexplained cytopenias have a risk of progression to clonal myeloid neoplasms, including myelodysplastic syndromes (MDS). If a somatic mutation in a gene associated with leukemia is detectable in hematopoietic tissue, especially if multiple mutations with a high (> 10%) variant allele frequency are present, the risk of progression to frank neoplasia is greater than if such mutations are not detected. These patients can be described with the term, “clonal cytopenias of undetermined significance” (CCUS). CCUS patients have a natural history similar to lower-risk MDS.


For patients with unexplained cytopenias, longitudinal follow-up including serial monitoring of blood counts is appropriate in view of the progression risk. Genetic testing may aid in risk stratification.


Cytopenias Next-generation sequencing Myelodysplastic syndromes Clonal hematopoiesis Ineffective hematopoiesis Diagnostic testing 


Compliance with Ethical Standards

Conflict of Interest

Dr. Steensma declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Dana-Farber Cancer Institute, Center for Prevention of Progression of Hematological Malignancies, Edward P. Evans Center for Myelodysplastic SyndromesHarvard Medical SchoolBostonUSA

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