Chronic myelomonocytic leukemia (CMML) belongs to the myelodysplastic/myeloproliferative neoplams according to WHO classification . CMML is characterized by a persistent monocytosis >1.0x109/L, signs of dysplasia in one or more cell lines as well as less than 20% blasts in the blood and bone marrow. BCR-ABL fusion gene and rearranged PDGFRA or PDGFRB gene must be absent.
CMML is a disease of elderly people with an average age of 65 and 70 years. The incidence is not exactly known, but might be around 1/100'000/year. Patients suffer from fatigue, loss of weight, fever, and night sweats. The majority of pateints presents at diagnosis as an atypical myeloproliferative syndrome with increased leukocytes, neutrophils and most of all monocytes. In a small part of patients, leukopenia and neutropenia prevails and the climical picture resembles more a myelodysplastic syndrome.
The persistent monozytosis >1.0 x 109/L in the peripheral blood is the main characteristic of the disease. Monocyte counts are often between 2-5 x 109/L, but can also reach numbers >80 x 109/L . Monocytes represent in most cases >10% of all peripheral leukocytes. Cytologically, monocytes look mature and inconspicuous. Occasionally, they show signs of impaired cell maturation such as abnormal granualtion and lobulated nuclei. These cells are called atypical monocytes. Blasts and promyelocytes may not exceed 20% (otherwise an acute myelocytic leukemia (AML) must be diagnosed). Leukopenia and neutropenia may be present. More frequently, a marked neutrocytosis is found besides the moncytosis. Anemia and thrombozytopenia may occur. Neutrophils can be clearly dysplastic.
The bone marrow is predominantly hypercellular with increased granulopoiesis and monopoiesis. Typically, distinct signs of dysplasia are found in the granulopoiesis in almost all cases, in about half of the cases in erythropoiesis and in about 80% of cases in the megakaryopoiesis. Light to modest reticulinic fibrosis is present in 30% of patients. In bone marrow biopsy, nodular foci of plasmocytoid, dendritic cells are found in 20% of cases.
According to WHO classifcation, the following five criteria have to be fulfilled for the diagnosis of CMML :
- Persistent monocytosis >1.0x109/L
- BCR-ABL negative
- No rearrangement of PDGFRA or PDGFRB
- Less thans 20% blasts (including promyelocytes) in the blood and the bone marrow
- Signs of dysplasia in 1 or more myeloicytic cell lines.
Based on the percentage of blasts, CMML-1 (<5% in blood, <10% in bone marrow) can be differentiated from CMML-2 (15-20% in blood, 10-20% in bone marrow) with a poorer prognosis.