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MYELODYSPLASTIC NEOPLASM

Should we give oligomonocytic chronic myelomonocytic leukemia a higher prominence in the next WHO Classification of Haematolymphoid Tumors?

Leukemia volume 37, pages 250–251 (2023)Cite this article

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Both the 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumors [1] and the new International Consensus Classification (ICC) [2] include a series of changes with respect to the 2017 WHO classification with implications for the definition, classification and prognostic stratification of hematological neoplasms. The different categories in which the different hematological diseases are subclassified are due to biological (i.e.: morphology, immunophenotype, and genetic features) and prognostic differences. Thus, an adequate classification aims to contain diseases that are clearly defined, clinically distinctive and non-overlapping.

Chronic myelomonocytic leukemia (CMML) has undergone different changes that affect both its diagnostic criteria and the subcategories into which it is divided. For instance, it has been decided to eliminate the blast-based subgroup of CMML-0 (<2% blasts in blood and <5% blasts in bone marrow and no Auer-rods) that appeared for the first time in the 2017 WHO classification and to return to the 2008 WHO classification definitions that divided CMML into CMML-1 and CMML-2 [1, 2]. The evidence has demonstrated that the addition of CMML-0 category to the previous CMML-1 and CMML-2 provided no or limited prognostic significance [3, 4]. Recently, all those myelodysplastic neoplasms (MDS) or MDS/MPN unclassifiable cases with relative monocytosis (≥10% monocytes) and a total monocyte count of 0.5 to ≤1 × 109/L have been categorized as oligomonocytic chronic myelomonocytic leukemia (OM-CMML) [5, 6]. Different studies have shown that these patients show similar clinical, genomic and immunophenotypic features than overt CMML [5, 7,8,9,10,11] and consequently, the upcoming 5th edition of the WHO [1] and ICC [2] classifications have lowered the cutoff for absolute monocytosis from 1.0 × 109/L to 0.5 × 109/L to incorporate cases diagnosed with OM-CMML. Therefore, the minimum diagnostic criterion to consider the diagnosis of CMML will be the presence of relative monocytosis associated with an absolute number of monocytes greater than or equal to 0.5 × 109/L [1, 2]. Although the reduction of the cutoff of absolute monocytosis seems to be an appropriate decision to integrate this subgroup of patients with clinical-biological characteristics much closer to CMML than to MDS [5, 7,8,9,10,11], the specific mention of OM-CMML as a disease could be a better decision as it would have prognostic implications. In the upcoming classifications, myelodysplastic CMML (MD-CMML) (WBC < 13 × 109/L) and myeloproliferative CMML (MP-CMML) (WBC ≥ 13 × 109/L) will be recognized as two disease subtypes given their distinctive clinical outcomes and genomic features [1, 2]. Recent data has shown the existence of an evolutionary continuum in CMML that begins in the OM-CMML stage and finishes in the MP-CMML stage [9]. These data are supported by the presence of a sequential increase in the proportion of RAS-pathway mutations, as it begins from initial stages of proliferation (i.e: OM-CMML), in which these mutations are practically absent, to intermediate (i.e.: MD -CMML) and terminal stages (i.e.: MP-CMML), in which RAS-pathway mutations are detected in approximately 60% of patients [9]. In addition, it has been shown that a high proportion of patients with OM-CMML progress to MD-CMML [5, 7, 8] and similarly, a high percentage of patients progress from MD-CMML to MP-CMML [9]. Specifically, with a median follow-up ranging from 12 to 31 months in the different series, 20% to 40% of patients with OM-CMML progressed to overt CMML [5, 7,8,9], and at a median follow-up of 46 months, 29% of patients with MD-CMML evolved to MP-CMML [9]. In this regard, three predictive factors of progression of OM-CMML into overt CMML have been identified: harboring more than three mutated genes, ASXL1 mutations and a relative monocytosis greater than 20% [9]. Moreover, OM-CMML had significantly longer overall survival and acute myeloid leukemia-free survival than did patients with CMML, considered as a whole group, and when compared with MD-CMML and MP-CMML [9]. Therefore, current data support that OM-CMML has a distinctive molecular profile with a very low incidence of RAS-pathway mutations and better clinical outcomes than MD-CMML and MP-CMML [9]. If these findings are prospectively validated by other groups in the coming years and the significance and potential clinical interest of defining OM-CMML as a new CMML subtype is corroborated, it would seem appropriate to recognize three disease subtypes of CMML in the upcoming classifications: OM-CMML, MD-CMML and MP-CMML.

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  1. Laboratori de Citologia Hematològica, Servei de Patologia, Grup de Recerca Translacional en Neoplàsies Hematològiques (GRETNHE), Hospital del Mar Research Institute (IMIM), Barcelona, Spain

    Xavier Calvo

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Calvo, X. Should we give oligomonocytic chronic myelomonocytic leukemia a higher prominence in the next WHO Classification of Haematolymphoid Tumors?. Leukemia 37, 250–251 (2023). https://doi.org/10.1038/s41375-022-01760-5

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