Clinical, molecular, and prognostic comparisons between CCUS and lower-risk MDS: a study of 187 molecularly annotated patients
Marissa Li, Moritz Binder, Terra L. Lasho, Alejandro Ferrer, Naseema Gangat, Aref Al‐Kali, Abhishek A. Mangaonkar, Michelle Elliott, Mark R. Litzow, William J. Hogan, Animesh Pardanani, Alexandra P. Wolanskyj, Matthew T. Howard, Rebecca L. King, Mithun Vinod Shah, Hassan B. Alkhateeb, Kebede H. Begna, Ayalew Tefferi, Christy M. Finke, Jennifer L. Oliveira, Rhett P. Ketterling, Horatiu Olteanu, Mrinal M. Patnaik
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