New clonal cytopenia risk prediction score
March 25, 2025
New Horizons in Leukemia Research:
Focus on Selected Papers
A recent study by Xie et al, published
in Blood, presents a model to predict the progression of clonal
cytopenia of undetermined significance (CCUS) to myeloid neoplasia (MN). The
researchers developed the Clonal Cytopenia Risk Score (CCRS), which is based on
three key factors. MLL Managing Director Prof. Dr. med. Torsten Haferlach
commented on the study in Blood.
Myeloid precursor lesions, such as clonal
hematopoiesis of undetermined potential (CHIP) and clonal cytopenia of
undetermined significance (CCUS), pose a clinical challenge because of the risk
of progression to myeloid neoplasia (MN). CCUS is characterized by persistent
cytopenias of undetermined etiology that persist for more than 4 months. It is
also defined by the detection of one or more chromosomal aberrations or somatic
mutations with an allele frequency of ≥ 2% (often in genes such as DNMT3A,
TET2 and ASXL1). However, the patients do not meet the diagnostic
criteria for MN as there is no significant dysplasia or increased blast count.
Although there are recent risk models that predict the risk of progression from
CHIP to MN, there is a lack of validated risk scores for CCUS based on large
cohorts.
Study results in detail:
In the November issue of Blood, Xie et al. presented the Clonal Cytopenia Risk Score (CCRS), an innovative risk assessment model. The study by Xie et al. analyzed 357 patients with CCUS from 17 academic centers and identified three major adverse prognostic factors: the presence of splicing mutations, a low platelet count (<100 x 10⁹/L), and the presence of two or more mutations (Figure 1). The CCRS is used to stratify patients into three risk groups: low, intermediate, and high. The 2-year cumulative incidence of MN was 6.4% for the low-risk group, 14.1% for the intermediate-risk group and 37.2% for the high-risk group.
Prof. Dr. med. Torsten Haferlach, Executive
Manager of the MLL, also published a commentary on this study in Blood.
According to Haferlach, the CCRS not only improves the predictive power, but
also opens new avenues for targeted or preventive therapeutic strategies that
can change the clinical management of patients with CCUS (Figure 2).
The score provides a more accurate assessment
of the risk of disease progression and could be valuable in the design and
comparison of future clinical trials. Prof. Dr. Dr. Haferlach emphasized that
the integration of genetic, clinical and molecular data is an important step
towards precision medicine and personalized therapy. This study is also an
example of how important it is to combine scientific data with
cross-institutional and international partnerships in order to expand the
common body of knowledge.
To learn more and access the full publications,
please visit the Blood website:
Xie Z et al. Risk prediction for clonal cytopenia:
multicenter real-world evidence. Blood. 2024. 144 (19): 2033–2044. Risk prediction for clonal cytopenia: multicenter real-world evidence |
Blood | American Society of Hematology (ashpublications.org)
Haferlach T.
A simple score for clonal cytopenias. Blood.
2024. 144 (19): 1981–1982. A simple score for clonal cytopenias | Blood | American Society of
Hematology (ashpublications.org)
The author
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Dr. rer. nat. Katharina Hörst