Leukaemia

Background

Leukaemias are clonal malignant disorders of the bone marrow characterised by the uncontrolled accumulation of abnormal white blood cells in the marrow and peripheral blood. They are broadly classified into:

• Acute leukaemias: Rapid onset and aggressive progression, involving immature precursors (blasts).
• Chronic leukaemias: Slower progression, often involving more mature or partially differentiated cells.

Pathophysiology of acute and chronic leukaemias
Acute leukaemias arise due to malignant transformation of haemopoietic stem or progenitor cells, leading to:

• Increased proliferation
• Reduced apoptosis
• Blocked cellular differentiation

This results in the accumulation of blast cells in the bone marrow. Acute leukaemia is typically defined by >20% blasts in the marrow (WHO classification) or presence of specific genetic abnormalities. Bone marrow failure is the dominant feature, with variable organ infiltration.

Chronic leukaemias involve the clonal proliferation of mature or maturing (differentiated) blood cells, rather than blasts. Unlike acute leukaemias, they are not defined by blast percentage, but typically show:

• A blast count <10% in both bone marrow and peripheral blood
• A more indolent clinical course, often with subtle or asymptomatic presentation
• The presence of mature or maturing cells on blood film and marrow
• Characteristic cytogenetic or molecular abnormalities, such as the Philadelphia chromosome (BCR-ABL1) in CML, and deletion 13q, trisomy 12, or IGHV mutation status in CLL.

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Acute Myeloid Leukaemia (AML)
Epidemiology:

• Most common acute leukaemia in adults
• Median onset ~65 years
• Rare in children (~10-15%)

Clinical features:

• Symptoms of bone marrow failure: anaemia, infection, bleeding
• Organ infiltration (e.g. skin, gums)

Investigations:

• Normochromic normocytic anaemia, thrombocytopenia
• Elevated or normal WBCs with circulating blasts
• Hypercellular marrow with >20% myeloblasts

Management:

• Supportive: transfusions, infection control, tumour lysis prevention
• Specific: chemotherapy ± stem cell transplant
• Remission defined by <5% blasts, recovery of counts

Prognosis:

• Dependent on age and cytogenetics
• ~30–40% long-term cure in younger adults; <10% in patients >70 years.

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Acute Lymphoblastic Leukaemia (ALL)
Epidemiology:

• Most common childhood cancer
• Peak incidence 3–7 years
• Secondary rise in adults >40 years

Clinical features:

• Bone marrow failure: pallor, fever, bleeding
• Organ infiltration: lymphadenopathy, hepatosplenomegaly, bone pain, CNS involvement (headache, cranial nerve signs), testicular involvement

Investigations:

• Anaemia, thrombocytopenia, blast cells on film
• WCC may be high due to blasts, but neutropenia is often present due to marrow suppression
• > 20% lymphoblasts in marrow
• CSF analysis with intrathecal chemotherapy
• Biochemical: ↑LDH, uric acid; imaging for masses

Management:

• Children: chemotherapy ± radiotherapy tailored to age/gender/WBC count
• Adults: similar, but with lower cure rates

Prognosis:

• ~90% cure rate in children; ~5–10% in adults >70 years.

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Chronic Myeloid Leukaemia (CML)
Incidence:

• ~15% of leukaemias
• Peak age 40–60 years.
• Associated with the Philadelphia chromosome (BCR-ABL1 fusion gene).

Clinical features:
Often asymptomatic. Symptomatic patients may report:

• Weight loss, night sweats, fatigue
• Splenomegaly
• Gout/uric acid symptoms

Investigations:

• Marked leucocytosis (neutrophils, myelocytes)
• Basophilia, anaemia, possible thrombocytosis
• Ph+ chromosome in ~95% on cytogenetics

Management:

• Tyrosine kinase inhibitors (TKIs e.g. imatinib)
• Allogeneic stem cell transplant in select cases

Prognosis:

• Excellent with TKI therapy—>90% long-term disease control.

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Chronic Lymphocytic Leukaemia (CLL)
Epidemiology:

• Most common leukaemia in the West
• Peak age 60–80 years.
• Male predominance (2:1)

Clinical features:

• Often incidental diagnosis
• Lymphadenopathy, splenomegaly
• Anaemia, thrombocytopenia
• Recurrent infections due to immunosuppression

Investigations:

• Lymphocytosis with clonal B-cells
• Normocytic anaemia, thrombocytopenia
• Marrow replacement by lymphocytes
• ↓Immunoglobulins, +autoimmune haemolysis in some

Management:

• Conservative in early stages
• Chemotherapy and anti-CD20 antibodies if symptomatic or progressive

Prognosis:
Variable course. Many live for years without treatment; disease is typically incurable.

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Summary Table

ED considerations
Acute leukaemias may present as life-threatening emergencies in the ED. Key complications include febrile neutropenia, tumour lysis syndrome, leukostasis, and CNS involvement. Prompt supportive care and urgent haematology referral are critical.