Chronic lymphocytic leukaemia — Rapid

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.
Before each treatment line, test TP53 mutation and del(17p); assess IGHV status before first treatment because these results change selection and should not be inferred from age or stage.
Targeted therapy has replaced routine chemoimmunotherapy for most adults; choose continuous BTK inhibition or fixed-duration venetoclax-based treatment from genetics, cardiac, bleeding, renal and interaction risk.
Venetoclax begins with a five-week 20, 50, 100, 200 and 400 mg daily ramp because rapid BCL2 inhibition can cause fatal tumour lysis.
Vaccinate early with non-live vaccines, screen hepatitis B before anti-CD20 therapy and assess recurrent serious infection with hypogammaglobulinaemia for prophylaxis or immunoglobulin replacement.
Rapid discordant node growth or high LDH is not routine CLL progression: use PET-CT to choose an adequate biopsy site for suspected Richter transformation.

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.

Rapid node growth, new severe B symptoms, extranodal mass or disproportionate LDH rise suggests Richter transformation and requires urgent PET-directed biopsy.

Jaundice, dark urine, falling haemoglobin, reticulocytosis or major thrombocytopenic bleeding suggests autoimmune cytopenia and needs same-day haematology assessment.

Richter pattern

A rapidly enlarging focal node, severe B symptoms or sharp LDH increase should trigger urgent transformation assessment.

Investigation priorities

First-line: FBC, film and flow cytometryFirst stepFirst line

Confirm persistent clonal B lymphocytosis and characteristic phenotype.

Management branches

New persistent lymphocytosisConfirm clone and classification

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.
Classify CLL, SLL or monoclonal B-cell lymphocytosis and set active monitoring or a treatment-indication assessment.

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.Reduce to 80 mg once daily with a strong CYP3A inhibitor or 80 mg twice daily with a moderate inhibitor and avoid strong inducers. Monitor bleeding, rhythm, blood pressure, infection, monthly FBC and skin; withhold 3 to 7 days around surgery and monitor closely when CrCl is below 30 mL/min or during dialysis. Avoid pregnancy, add barrier contraception to hormonal methods and continue effective contraception for 1 month after treatment; stop breastfeeding.

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.Classify tumour-lysis risk from nodes, lymphocyte count and renal function and use timed hydration, urate lowering and chemistry. Strong CYP3A inhibitors are contraindicated during ramp-up; review CYP3A and P-gp dose changes throughout and interrupt rather than guessing after a prolonged missed course. Avoid pregnancy, use effective contraception during and for 30 days after treatment, stop breastfeeding and discuss possible male fertility impairment.

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