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.

Characteristics and long‐term outcome in a large series of chronic myelomonocytic leukaemia patients including 104 formerly referred to as oligomonocytic

“…The median time to transformation to C-CMML was 17.8 months in our OM-CMML patients. While previous studies have reported CIPs from OM-CMML to C-CMML of 18%-40%, 3,6,8,9 the 5-year CIP to C-CMML was higher in our study (47%), presumably due to the longer follow-up of our patients, suggesting that approximately half of OM-CMML patients will evolve to C-CMML. The CIP to AML was lower in our OM-CMML patients (11%) than in the MD-CMML or MP-CMML patients, which is in line with previous reports.…”

“…With this change, what was formerly known as oligomonocytic (OM)-CMML is now included in the classical (C)-CMML category. This modification was based on similarities between OM-CMML and C-CMML [3][4][5][6][7][8] observed in a small series of patients. OM-CMML has superior outcomes to C-CMML, 8,9 although it is unclear whether this benefit is independent of CPSS.…”

“…This modification was based on similarities between OM-CMML and C-CMML [3][4][5][6][7][8] observed in a small series of patients. OM-CMML has superior outcomes to C-CMML, 8,9 although it is unclear whether this benefit is independent of CPSS. Importantly, there is scarce information on follow-up, management and outcome of OM-CMML patients.…”

Sex‐associated differences in genomic profile of chronic myelomonocytic leukemia involving differential representation of SRSF2 gene mutation

“…A comprehensive explanation of the morphological assessment, Next-Generation sequencing (NGS) methodology, and flow cytometry analysis of monocyte subsets have been previously described by our group. 7,8 In our series, we observed a higher proportion of men (145/240; 60%) than women (95/240; 40%). The main differences between women and men in our series are depicted in Table 1.…”

Progression in Myeloid Neoplasms: Beyond the Myeloblast

“…If monocytosis is ≥1 × 10 9 /L, only one supporting criterion is necessary for the diagnosis of CMML [1, 2]. Interestingly, recent data suggest the existence of an evolutionary continuum even within CMML itself, from oligomonocytic CMML over dysplastic-type CMML to proliferative-type CMML, which is linked to acquisition of prognostically adverse ASXL1 , CBL , and/or RAS-pathway mutations [82].…”