Clinical, molecular, and prognostic comparisons between CCUS and lower-risk MDS: a study of 187 molecularly annotated patients

Abstract

Clonal cytopenia of undetermined significance (CCUS) is defined by the presence of somatic driver mutations/copy number alterations (CNA) in hematopoietic cells, in patients with unexplained cytopenia in 1 or more peripheral blood (PB)-cell lineages, in the absence of overt morphologic dysplasia, excess blasts, and myelodysplastic syndromes (MDS)-defining chromosomal abnormalities. 1,2 CCUS is associated with an increased risk for evolution to MDS and/or acute myeloid leukemia (AML), with somatic mutational variant allele frequency (VAF) $10%, or carrying $2 mutations, being associated with predictive values of 0.86 and 0.88 for diagnosis of a myeloid neoplasm. 1 In addition, dominant clone VAF .20% has been associated with a .95% risk of progression to a clinically apparent myeloid neoplasm in 10 years, raising the question as to whether these patients would better be classified as having an early myeloid neoplasm rather than CCUS. 3 These data, among others, have led to operational classification criteria for the diagnosis of CCUS that includes the presence of myeloid-relevant somatic mutations with a VAF $20%, without overt bone marrow (BM) dysplasia (,10% dysplastic cells). 2