Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Outcomes and molecular profile of oligomonocytic CMML support its consideration as the first stage in the CMML continuum.

Abstract

Oligomonocytic chronic myelomonocytic leukemia (OM-CMML) patients are currently classified into the different categories of the 2017 WHO MDS classification. However recent data support considering OM-CMML as a specific subtype of chronic myelomonocytic leukemia (CMML) given their similar clinical, genomic and immunophenotypic profiles. The main purpose of our study was to provide survival outcome data of a well-annotated series of 42 patients with OM-CMML and to compare them to 162 patients with CMML, 120 with dysplastic type (D-CMML) and 42 with proliferative type (P-CMML). OM-CMML showed significantly longer overall survival (OS) and acute myeloid leukemia-free survival than CMML patients considered as a whole group, and when compared to D-CMML and P-CMML, respectively. Moreover, gene mutations associated with increased proliferation (i.e.: ASXL1 and RAS-pathway mutations) were identified as independent adverse prognostic factors for OS in our series. We found that at a median follow-up of 53.47 months, 29.3% of our OM-CMML patients progressed to D-CMML, and at a median follow-up of 46.03 months, 28.6% of our D-CMML progressed to P-CMML. These data support the existence of an evolutionary continuum among OM-CMML, D-CMML and P-CMML. In this context, we observed that harboring more than 3 mutated genes, ASXL1 mutations and a peripheral blood monocyte percentage above 20% significantly predicted shorter time of progression of OM-CMML into overt CMML. These variables were also detected as independent adverse prognostic factors for OS in OM-CMML. These data support the consideration of OM-CMML as the first evolutionary stage within the proliferative continuum of CMML.