How I investigate chronic myelomonocytic leukemia

Abstract

The 2016 revised 4th edition of the World Health Organization classification of hematopoietic neoplasms updated the diagnostic criteria for chronic myelomonocytic leukemia (CMML). Persistent peripheral blood monocytosis of at least 1 × 109/L and a percentage of monocytes ≥10% of the circulating white blood cell count (WBC) are both prerequisite criteria for this diagnosis. CMML represents the prototype of “overlapping” myeloid neoplasms with concurrent myeloproliferative and myelodysplastic features. However, clinical presentation is heterogeneous, with cases showing prevailing “dysplastic” features and others a predominant “proliferative” phenotype. Accounting for this diversity, two variants of CMML are recognized: “dysplastic” CMML defined by WBC < 13 × 109/L and “proliferative” CMML with WBC ≥ 13 × 109/L often showing features mimicking a myeloproliferative neoplasm. Although not an official WHO category, the “oligomonocytic” variant of CMML is defined by relative monocytosis with an absolute monocyte count of 0.5‐0.9 × 109/L. It can be considered a “pre‐phase,” as it frequently anticipates the development of an overt, classic CMML. In an attempt at improving disease prognostication, the blast count based grading system for CMML of the WHO 2008 Classification has been expanded in 2016 to include a new “CMML‐0” category. Lastly, the large body of knowledge on the molecular events occurring in CMML has been used to assist diagnosis and assess prognosis. Despite the step forwards, diagnosis of CMML still remains one of exclusion as no clinical, pathologic or molecular findings are specific for this disease. The current review brings insight into the spectrum of CMML and provides practical advice to approach suspected cases of CMML.

To Treat or Not to Treat: A Case of Simultaneous Discovery of Chronic Myelomonocytic Leukemia and Multiple Myeloma

“…These results were consistent with a diagnosis of CMML and plasma cell dyscrasia, i.e. MM [ 3 , 4 ]. On admission, he had received a unit of packed red blood cells for his anemia.…”

“…The coexistence of MM and CMML is an extremely rare event. There are three case reports in the literature that have discussed this finding [ 3 , 4 ]. However, there have been case reports where patient being treated with an alkylating agent for MM later developed CMML.…”

Treatment Outcomes and Prognostic Factors in 66 Patients with Chronic Myelomonocytic Leukemia (CMML) in a Single Center

“…17 There are several criteria used in clinic to diagnose CMML, such as persistent absolute monocytosis of ≥1 × 10 9 /L, with monocytes accounting for more than 10% in peripheral blood, dysplasia in one or more bone marrow cell lineage, and the absence of genetic rearrangements in the PDGFRA, FDGFRB, and FGFR1 genes and the PCM1-JAK2 and BCR-ABL1 fusions. 17,18 According to the leukocyte count of 13×10 9 /L, CMML is subdivided into myelodysplastic (MD) and myeloproliferative (MP) variants. 19 Outcomes of patients with MP CMML are worse than those of patients with MD CMML.…”

“… 17 There are several criteria used in clinic to diagnose CMML, such as persistent absolute monocytosis of ≥1 × 10 9 /L, with monocytes accounting for more than 10% in peripheral blood, dysplasia in one or more bone marrow cell lineage, and the absence of genetic rearrangements in the PDGFRA, FDGFRB , and FGFR1 genes and the PCM1-JAK2 and BCR-ABL1 fusions. 17 , 18 …”

Mouse Models of CMML

“…Diagnosis of CMML is complicated due to overlapping MDS and MPN features, the high heterogeneity of clinical presentation, and the absence of specific indicators for CMML [ 13 ]. There are several criteria used in the clinic to diagnose CMML, such as persistent absolute monocytosis (≥1 × 10 9 /L), with monocytes accounting for more than 10% but less than 20% of leucocytes (WBC—white blood cells) in the peripheral blood, dysplasia in one or more bone marrow (BM) cell lineage, and the absence of genetic rearrangements in the PDGFRA , FDGFRB , and FGFR1 genes and the PCM1-JAK2 and BCR-ABL1 fusions [ 13 , 14 , 15 ] ( Figure 1 ).…”