Chronic myelomonocytic leukemia: 2022 update on diagnosis, risk stratification, and management

Abstract

Disease Overview: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, with an inherent risk for leukemic transformation (~15% over 3-5 years). Diagnosis:Diagnosis is based on the presence of sustained (>3 months) peripheral blood monocytosis (≥1 Â 10 9 /L; monocytes ≥10%), usually with accompanying bone marrow dysplasia. Clonal cytogenetic abnormalities occur in ~30% of patients, while >90% have somatic gene mutations. Mutations involving TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%), and the oncogenic RAS pathway (~30%) are frequent, while the presence of ASXL1 and DNMT3A mutations and the absence of TET2 mutations negatively impact overall survival. Risk-Stratification: Molecularly integrated prognostic models include the Groupe Français des Myélodysplasies, Mayo Molecular Model (MMM), and the CMML specific prognostic model. Risk factors incorporated into the MMM include presence of truncating ASXL1 mutations, absolute monocyte count >10 Â 10 9 /L, hemoglobin <10 g/dL, platelet count <100 Â 10 9 /L, and the presence of circulating immature myeloid cells. The MMM stratifies CMML patients into four groups: high (≥3 risk factors), intermediate-2 (2 risk factors), intermediate-1 (1 risk factor), and low (no risk factors), with median survivals of 16, 31, 59, and 97 months, respectively.Risk-adapted therapy: Hypomethylating agents such as 5-azacitidine and decitabine are commonly used, with overall response rates of ~40%-50% and complete remission rates of ~7%-17%; with no impact on mutational allele burdens. Allogeneic stem cell transplant is the only potentially curative option but is associated with significant morbidity and mortality.

Plasmacytoid Dendritic Cells, a Novel Target in Myeloid Neoplasms

“…CMML is characterized by sustained monocytosis and an overlap of myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) resulting from a cumulative mutational landscape including TET2 (60%), SRSF2 (50%), ASXL1 (40%), and the oncogenic RAS pathway (30%) mutations [ 103 ]. Median overall survival of CMML patients range between 16 and 97 months depending on several scores, such as the Mayo Molecular Model score, and between 15 and 30% of patients die from a leukemic transformation in AML.…”

“…ASXL1 , NRAS , SETBP1 , and RUNX1 mutations are independently associated with inferior overall survival [ 104 ]. There is usually an increased monocytic population in the classical monocytes fraction (CD14 + /CD16 − ) which also express other monocytic markers (CCR2, CD36, HLA-DR, and CD11c) and a low level of CX3CR1 [ 103 , 105 ].…”

Real-World Data on Chronic Myelomonocytic Leukemia: Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes

“…AlloSCT is the only treatment option with proven curative capacity, although 5-year OS after alloSCT is still only 20–50% [ 17 , 18 , 19 , 20 , 21 ]. Moreover, in fact, due mainly to the older age and comorbidities of most CMML patients, alloSCT is only feasible in around 10% of patients [ 22 , 23 ].…”

Hematoma Formation After Hip Corticosteroid Injection in a Patient with Chronic Myelomonocytic Leukemia

“…Diagnosis is made with peripheral blood flow cytometry and is confirmed with bone marrow biopsy. It is treated with hydroxyurea and hypomethylating agents, with studies investigating new monoclonal antibody therapies; however, stem cell transplant is the only currently available treatment that is associated with durable remission 10,11 .…”

“…Presentation is variable, with features of myelodysplastic syndromes (MDS), including peripheral blood cytopenias and easy bruising and features of myeloproliferative neoplastic features including “B symptoms” such as fatigue, bone pain, weight loss, and night sweats as well as hepatosplenomegaly. Patients with CMML have a 15% to 30% risk of transformation to acute myeloid leukemia, which carries additional risk of hemorrhage 10 . Importantly, 20% of patients with CMML can have systemic inflammatory disease such as idiopathic thrombocytopenic purpura or rheumatoid arthritis 11 .…”