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

Calvo González, Xavier; Roman-Bravo, David; García Gisbert, Nieves, 1994-; Rodriguez-Sevilla, Juan José; Garcia-Avila, Sara; Florensa Brichs, Lourdes; Gibert Fernandez, Joan, 1988-; Fernández Rodríguez, M. Concepción; Salido Galeote, Marta; Puiggros Metje, Anna Maria; Espinet Solà, Blanca; Colomo Saperas, Luis Alberto; Bellosillo Paricio, Beatriz; Ferrer, Ana; Arenillas Rocha, Leonor

doi:http://dx.doi.org/10.1182/bloodadvances.2022007359

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

Llicència

Citació

Calvo X, Roman-Bravo D, Garcia-Gisbert N, Rodriguez-Sevilla JJ, Garcia-Avila S, Florensa L, et al. Outcomes and molecular profile of oligomonocytic CMML support its consideration as the first stage in the CMML continuum. Blood Adv. 2022 Jul 12; 6(13): 3921-31. DOI: 10.1182/bloodadvances.2022007359

Resum

atients with oligomonocytic chronic myelomonocytic leukemia (OM-CMML) are currently classified according to the 2017 World Health Organization myelodysplastic syndromes 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 had significantly longer overall survival (OS) and acute myeloid leukemia-free survival than did patients with CMML, considered as a whole group, and when compared with D-CMML and P-CMML. Moreover, gene mutations associated with increased proliferation (ie, 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 patients with OM-CMML progressed to D-CMML, and at a median follow-up of 46.03 months, 28.6% of our D-CMML group progressed to P-CMML. These data support the existence of an evolutionary continuum of OM-CMML, D-CMML, and P-CMML. In this context, we observed that harboring more than 3 mutated genes, carrying ASXL1 mutations, and a peripheral blood monocyte percentage >20% significantly predicted a 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.