DUBROVNIK, CROATIA – in 2018.
Even with updated World Health Organization (WHO) criteria, karyotyping, and genetic analyses, it can be difficult to distinguish CMML from other conditions, according to Nadira Durakovic, MD, PhD, of the University Hospital Centre Zagreb (Croatia).
However, there are characteristics that differentiate CMML from myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPNs), and atypical chronic myeloid leukemia (CML), Dr. Durakovic said at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.
Studies have suggested that monocyte subset distribution analysis can be useful for diagnosing CMML.
According to the 2016 WHO classification, patients have CMML if:
- They have persistent peripheral blood monocytosis (1×109/L), with monocytes accounting for 10% of the white blood cell count.
- They do not meet WHO criteria for BCR-ABL1-positive CML, primary myelofibrosis, polycythemia vera, or essential thrombocythemia.
- There is no evidence of PCM1-JAK2 or PDGFRA, PDGFRB, or FGFR1 rearrangement.
- They have fewer than 20% blasts in the blood and bone marrow they have dysplasia in one or more myeloid lineages.
If myelodysplasia is absent or minimal, an acquired clonal cytogenetic or molecular genetic abnormality must be present. Alternatively, if patients have monocytosis that has persisted for at least 3 months, and all other causes of monocytosis have been excluded, “you can say that your patient has CMML,” Dr. Durakovic said.
Other causes of monocytosis include infections, malignancies, medications, inflammatory conditions, and other conditions, such as pregnancy.
However, Dr. Durakovic pointed out that the cause of monocytosis cannot always be determined, and, in some cases, CMML patients may not meet the WHO criteria.
“There are cases where there just aren’t enough monocytes to fulfill the WHO criteria,” Dr. Durakovic said. “You can have a patient with peripheral blood cytopenia and monocytosis who does not have 1,000 monocytes. Patients can have progressive dysplasia, can have splenomegaly, be really sick, but fail to meet WHO criteria.”
Differential diagnosis
“Differentiating CMML from myelodysplastic syndromes can be tough,” Dr. Durakovic said. “There are dysplastic features that are present in CMML ... but, in CMML, they are more subtle, and they are more difficult to appreciate than in myelodysplastic syndromes.”
The ratio of myeloid to erythroid cells is elevated in CMML, and patients may have atypical monocytes (paramyeloid cells) that are unique to CMML.
Dr. Durakovic noted that megakaryocyte dysplasia in CMML can be characterized by “myeloproliferative megakaryocytes,” which are large cells that cluster and have hyperlobulated nuclei, or “MDS megakaryocytes,” which are small, solitary cells with hypolobulated nuclei.
She noted that “MPN phenotype” CMML is characterized by leukocytosis, monocytosis, hepatomegaly, splenomegaly, and clinical features of myeloproliferation (fatigue, night sweats, bone pain, weight loss, etc.).
Thirty percent of cases are associated with splenomegaly, and 30% of patients can have an increase in bone marrow reticulin fibrosis.
Dr. Durakovic also noted that a prior MPN diagnosis excludes CMML. The presence of common MPN mutations, such as JAK2, CALR, or MPL, suggests a patient has an MPN with monocytosis rather than CMML.
Patients who have unclassified MPNs or MDS, rather than CMML, either do not have 1,000 monocytes or the monocytes do not represent more than 10% of the differential, Dr. Durakovic said.
It can also be difficult to differentiate CMML from atypical CML.
“Atypical CML is characterized by profound dysgranulopoiesis, absence of the BCR-ABL1 fusion gene, and neutrophilia,” Dr. Durakovic explained. “Those patients [commonly] have monocytosis, but, here, that 10% rule is valuable because their monocytes comprise less than 10% of the entire white blood cell count.”