WHO criteria
The WHO criteria for diagnosis are as follows:
Persistent peripheral blood monocytosis with counts >1x109/L
No Philadelphia chromosome or BCR-ABL1 fusion gene
No rearrangement of PDGFRA or PDGFRB gene
<20% myeloblasts, monoblasts and promonocytes in peripheral blood or bone marrow
Dysplasia in one or more of the myeloid lineages; if myelodysplasia is absent or minimal then a diagnosis of CMML can be made if other requirements are met and:
A molecular genetic abnormality is present in haematopoietic cells, or
Monocytosis present for ≥3 months and other causes of monocytosis have been ruled outWHO defined CMML has two main subsets, CMML-1 and CMML-2. CMML-1 is diagnosed if myeloblasts, monoblasts and promonocytes are <5% of peripheral blood and <10% of bone marrow. CMML-2 is diagnosed if:

Myeloblasts, monoblasts or promonocytes are 5-19% in blood, or
Myeloblasts, monoblasts or promonocytes are 10-19% in bone marrow, or
Auer rods are presentCMML-1 and CMML-2 can be additionally grouped as CMML-1 or CMML-2 with eosinophilia. These are diagnosed if the above criteria are met and the blood eosinophil count is >1.5x109/L.Presence of two or more phenotypic abnormalities can aid a diagnosis of CMML in the absence of identifying cytogenetic or dysplastic features. These can include the expression of CD56 and/or CD2, or under-expression of HLA-DR.

Prognosis
Factors affecting prognosis
CMML-2 has a reduced overall survival as compared with CMML-1, with median survivals of 15 and 20 months, respectively. Myeloproliferative CMML (>13x109 monocytes/L) has a reduced survival compared with myelodysplastic CMML. A platelet count of <100 x109/L reduces overall survival. A haemoglobin level of <10g/dL has a reduced overall survival.
Anderson Cancer Center found that a haemoglobin level of <12g/dL, total circulating lymphocyte count of >2.5 x 109/L, >0% immature myeloid cells, >10% bone marrow blasts causes a reduced overall survival. This data allows cases of CMML to be stratified into low, intermediate-1, intermediate-2 and high risk groups. These groups have median survival times of 24, 15, 8 and 5 months respectively. The Düsseldorf score
The Düsseldorf score stratifies cases using four categories, giving one point for each; bone marrow blasts ≥5%, LDH >200U/L, haemoglobin ≤9g/dL and a platelet count ≤100,000/uL. A score of 0 indicates a low risk group 1-2 indicates an intermediate risk group and 3-4 indicates a high risk group. The cumulative 2 year survival of scores 0, 1-2 and 3-4 is 91%, 52% and 9%; and risk of AML transformation is 0%, 19% and 54% respectively. Treatment
The treatment of CMML remains challenging due to the lack of clinical trials investigating the disease as its own clinical entity. It is often grouped with MDS in clinical trials, and for this reason the treatment of CMML is very similar to that of MDS. Most cases are dealt with as supportive rather than curative because most therapies do not effectively increase survival.