Myeloid Neoplasms With Oligomonocytosis Exhibit Heterogenous Pathologic and Genetic Features

The criteria used to classify patients with myeloid neoplasms and monocytosis have changed in the fifth edition of the World Health Organization classification (WHO5) and the International Consensus Classification (ICC). Although both classifications have reduced the absolute monocyte count threshold for chronic myelomonocytic leukemia (CMML) to 0.5 × 10⁹/L, the ICC has also introduced new morphologic criteria for CMML. We studied the effect of these changes on a large cohort of myeloid neoplasms with white blood cell count < 13 × 10⁹/L and blasts <20% that were previously classified using the fourth revised edition of the WHO classification of hematologic malignancies (WHO4r). The lower monocyte threshold might reclassify approximately 20% of WHO4r-defined myelodysplastic syndrome as myelodysplastic-type CMML (MD-CMML) in the new classifications. This change led to an 84% increase in MD-CMML by WHO5 criteria. The number of MD-CMML cases in the cohort decreases from 107 by WHO5 criteria to 40 by ICC criteria because of the morphologic criteria. New ICC criteria remove 55% of WHO4r-defined MD-CMML patients from the category, and these and other patients (13% of our cohort) are not classifiable by ICC criteria. ICC-defined CMML enriches for CMML-like genetic signatures, but we find that genetic classification and genetically informed risk models predict outcome better than monocyte counts or morphologic features.