Chronic Myelomonocytic Leukaemia: Diagnosis, Risk and Treatment

Chronic myelomonocytic leukaemia (CMML) is the commonest of the myelodysplastic/myeloproliferative overlap disorders: it combines features of bone marrow failure — low counts, abnormal cell development — with over-production of monocytes. It occurs mainly in older adults, with an annual incidence of roughly three to four per 100,000, and it behaves very differently between patients. The 2021 Chinese guideline from the Chinese Society of Hematology sets out the diagnostic work-up, classification, prognostic scoring and treatment.

How it is diagnosed

The essential tests are a full blood count, a bone marrow aspirate with a differential count — at least 100 white cells on the peripheral film and 200–500 nucleated cells on the marrow — and a bone marrow biopsy. Persistent absolute monocytosis in the blood is the defining feature, and the guideline requires distinguishing mature from immature (abnormal) monocytes, since the immature fraction carries prognostic weight. Dysplasia in one or more cell lines, assessment of blasts — including myeloblasts, monoblasts and promonocytes, with cytochemical staining such as non-specific esterase used to confirm monocytic cells — and exclusion of other causes of monocytosis, including infection, inflammation, autoimmune disease and other myeloid neoplasms, complete the diagnosis.

Classification and molecular testing

CMML is divided by blast percentage into CMML-1 and CMML-2, and by white cell count into dysplastic and proliferative subtypes — a distinction that reflects whether cytopenias or over-production dominate, and which influences treatment. Cytogenetics and, critically, next-generation sequencing are recommended: mutations in ASXL1, TET2, SRSF2, SETBP1, RAS pathway genes and others inform both prognosis and, increasingly, treatment choice. The guideline reflects updated international minimum diagnostic criteria that recognise typical, variant and pre-CMML presentations.

Prognosis

Risk stratification uses validated scoring systems. The guideline recommends MD Anderson or CMML-specific prognostic scoring when mutation results are unavailable, and the molecularly integrated systems — CPSS-mol or the Mayo molecular model — when they are available, because they discriminate better. Prognosis ranges widely, from near-normal life expectancy in low-risk disease to a median survival measured in one to two years in high-risk disease, and the risk score is what drives the treatment decision.

Treatment

Low-risk, asymptomatic patients are observed with regular blood counts and clinical review — treatment does not change the course and adds toxicity. Patients with symptomatic cytopenias are treated with supportive care: transfusions, growth factors for infection risk, and erythropoiesis-stimulating agents for anaemia in selected patients. Disease-modifying treatment with hypomethylating agents — azacitidine or decitabine — is used for patients with higher blast counts or progressive disease, and can produce meaningful responses and, in some patients, durable disease control; hydroxyurea controls high white cell counts and spleen enlargement in proliferative disease. Allogeneic stem cell transplantation remains the only potentially curative treatment and is recommended for eligible higher-risk patients — eligibility being limited in practice by the age and comorbidity profile of most patients with CMML.

Practical guidance

Ask for the specific subtype, blast percentage, cytogenetics and mutation profile, and which prognostic score applies. Confirm that reactive causes of monocytosis have been excluded. Ask whether observation, hypomethylating therapy or transplant assessment is appropriate, and — if transplant is a possibility — ask for the referral early, because donor search and fitness assessment take time. Keep a simple record of blood counts over time; the trajectory is often the most useful information at clinic visits.