Synopsis
Confirm chronic lymphocytic leukaemia, separate it from monoclonal B-cell lymphocytosis and other lymphomas, recognise treatment indications and prevent infectious, autoimmune and tumour-lysis harm.
- CLL requires at least 5 × 10⁹/L clonal B lymphocytes in peripheral blood persisting for at least 3 months with a characteristic flow phenotype.
- First-line confirmation is blood film and flow cytometry showing a light-chain-restricted CD19-positive, CD5-positive, CD23-positive B-cell population with weak CD20 and surface immunoglobulin.
- Do not treat an asymptomatic lymphocyte count: active monitoring is first-line until marrow failure, symptomatic or progressive tissue disease, refractory autoimmune cytopenia or defined B symptoms develop.
Key red flags
Fever, rigors, hypotension, confusion or hypoxia is sepsis until assessed; CLL causes functional antibody failure even before treatment and fever may be muted.
A rapidly enlarging focal node, severe B symptoms or sharp LDH increase should trigger urgent transformation assessment.
Investigation priorities
Confirm persistent clonal B lymphocytosis and characteristic phenotype.
Management branches
Absolute lymphocytosis persists without a clear transient cause.
- Repeat FBC and examine the film, assess nodes, spleen, infection, cytopenia and symptoms.
- Perform flow cytometry and calculate the clonal B-cell count, expanding testing if phenotype is atypical.
Key medicines
ZanubrutinibGive 320 mg orally once daily or 160 mg orally twice daily continuously until progression or unacceptable toxicity; use 80 mg twice daily in severe Child-Pugh C hepatic impairment.
VenetoclaxRamp orally once daily over 5 weeks: 20 mg in week 1, 50 mg week 2, 100 mg week 3, 200 mg week 4 and 400 mg from week 5; then use 400 mg daily for the selected 12-cycle obinutuzumab regimen, 24-month rituximab regimen or until progression or intolerance for monotherapy.