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Oncology

Chronic Leukaemia (Adult Overview)

Malignant proliferation of mature-appearing blood cells, typically with a more indolent course than acute leukaemias. Main types in adults are Chronic Lymphocytic Leukaemia (CLL) and Chronic Myeloid Leukaemia (CML).

Also known as: CLL, CML

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Referral and warning signs

When to refer

Refer ALL suspected cases of chronic leukaemia to Haematologist/Oncologist for diagnosis confirmation, subtyping/risk stratification, and management.

Red flags

  • Marked lymphocytosis or high WBC count with immature forms/basophilia
  • Significant lymphadenopathy or massive splenomegaly
  • 'B' symptoms (fever, night sweats, weight loss)
  • Significant anaemia or thrombocytopenia
  • Symptoms of leukostasis (headache, vision change, dyspnoea, priapism) - EMERGENCY in CML

Signs and symptoms

  • Often asymptomatic initially, detected on routine blood count.
  • General Symptoms: Fatigue, weakness, malaise, anorexia, weight loss, night sweats, low-grade fever.
  • Chronic Lymphocytic Leukaemia (CLL): Lymphadenopathy (painless, generalized), Splenomegaly, Hepatomegaly, Increased infections (hypogammaglobulinemia), Autoimmune complications (haemolytic anaemia, ITP), Richter's transformation (rare progression).
  • Chronic Myeloid Leukaemia (CML): Splenomegaly (often massive, LUQ discomfort/early satiety), Hepatomegaly, Hypermetabolism symptoms (weight loss, sweats), Leukostasis symptoms (rare - headache, visual changes, dyspnoea, priapism), Bleeding/bruising (platelet dysfunction), Gout. Can progress to accelerated phase or blast crisis.

Risk factors

  • CLL: Older age, Male gender, Family history, Caucasian race.
  • CML: Exposure to high-dose ionizing radiation. Associated with Philadelphia chromosome (BCR-ABL1 fusion gene).

Diagnosis

Clinical assessment

Suspect based on persistent lymphocytosis (CLL) or high WBC count with immature granulocytes/basophilia (CML) on CBC, often with lymphadenopathy/splenomegaly.

Investigations

  • Complete Blood Count (CBC) with Differential and Peripheral Blood Film: CLL (Marked mature lymphocytosis, smudge cells). CML (High WBC, left shift, basophilia, eosinophilia).
  • Immunophenotyping (Flow Cytometry) on blood: Confirms CLL clonality/markers (CD5+, CD19+, CD20dim+, CD23+).
  • Bone Marrow Aspiration and Biopsy: Confirms diagnosis, cytogenetics.
  • Cytogenetics / Molecular Testing: CLL (Prognostic markers - del(17p) etc). CML (Requires Philadelphia chromosome / BCR-ABL1 detection).
  • Biochemistry: LDH, Uric acid, LFTs, RFTs. Beta-2 microglobulin (CLL prognosis). Coombs test (CLL).

Diagnostic criteria

CLL: Persistent monoclonal B-lymphocytosis (>5x10^9/L) with characteristic immunophenotype. CML: Characteristic blood/marrow findings + Detection of Philadelphia chromosome/BCR-ABL1 fusion.

Management

Non-pharmacological management

  • Referral to specialized Haematology/Oncology centre.
  • CLL: Watchful Waiting (early, asymptomatic). Supportive care (vaccinations, manage infections, IVIG).
  • CML: Treatment required from diagnosis. Allogeneic Stem Cell Transplantation (specific situations).

Pharmacological treatment

  • CLL (If treatment indicated): Chemo-immunotherapy (FCR, BR, Chlorambucil+Anti-CD20 Ab). Targeted Therapies (BTK inhibitors - Ibrutinib etc; BCL-2 inhibitors - Venetoclax).
  • CML: Tyrosine Kinase Inhibitors (TKIs): Mainstay (Imatinib, Dasatinib, Nilotinib etc). Target BCR-ABL1. Lifelong therapy usual.

Monitoring

CLL: Monitor CBC, nodes/spleen, symptoms. CML: Monitor CBC, BCR-ABL1 PCR levels (key marker), TKI side effects.

Complications

  • CLL: Infections, Autoimmune cytopenias, Richter's transformation, Hypogammaglobulinemia, Second malignancies.
  • CML: Progression (accelerated/blast phase), Leukostasis, Bleeding/thrombosis, Splenic infarct/rupture, Treatment side effects.

Prevention

  • Generally not preventable, avoid high-dose radiation for CML.

Patient education

  • Explain specific type (CLL vs CML) and chronic nature.
  • CLL: Explain 'watch and wait', treatment indications, infection risk.
  • CML: Explain BCR-ABL1 target, lifelong TKI importance and adherence, monitoring, side effects.
  • Need for regular follow-up.
  • When to seek medical attention.

Uganda-specific notes

CLL and CML occur. Diagnosis requires haematopathology, flow cytometry, and cytogenetics/molecular testing (BCR-ABL1) limited to specialized centres. Access to standard therapies (Rituximab, TKIs like Imatinib) improving but may still be challenging/costly.

References

  • Uganda Clinical Guidelines (UCG) 2023

    Chapter 12, Section 12.3.2 (Listed under Adult Cancers)

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