Acute Lymphoblastic Leukaemia

Malignant disease of primitive lymphoid cells (lymphoblasts)

Aetiology

• Most common childhood cancer, peaks around 2-4 years

• Can also affect adults over 45

• Often associated with Down syndrome

• Associated with the Philadelphia chromosome (t(9:22) translocation) in 30% of adults and 3-5% of children with ALL

Pathophysiology

• Occurs when there is malignant change in one of the lymphocyte precursor cells

• It causes acute proliferation of a single type of lymphocyte, usually B-lymphocytes

• Excessive proliferation of these cells causes them to replace the other cell types being created in the bone marrow, leading to a pancytopenia

Clinical presentation

• Marrow failure - anaemia, infections, bleeding

• Leukaemic effects (leukostasis) - high count with obstruction of circulation, involvement of areas outside the marrow and blood (extra-medullary) e.g. CNS, testis

• Bone pain

Classification

Type	Morphology
L1	Small, uniform blasts (children)
L2	Larger, heterogeneous blasts (adults)
L3	Burkitt-type (vacuolated)

 

Investigations

• Blood count and film
• Reduction in normal cells
• Presence of abnormal cells (‘blasts’) - large size, high nuclear:cytoplasmic ratio, prominent nucleolus
• By definition an acute leukaemia involves an excess of ‘blasts’ (≥20%) in either the peripheral blood or bone marrow

• Coagulation screen

• Bone marrow aspirate
• Morphology
• Immunophenotype
• Cyto/molecular genetics - diagnostic utility, prognostic significance
• Trephine - enables better assessment of cellularity and is helpful when aspirate is sub-optimal

Management

• Multi-agent chemotherapy - can least up to 2-3 years
• Different phases of treatment of varying intensity
• Targeted treatments in certain subsets
• Hickman line used to provide long-term central venous access

Complications

Complications of disease

• Anaemia

• Neutropenia
• Increased severity and duration of infections
• Gram negative bacteria can cause fulminant life-threatening sepsis in neutropenic patients
• Patients also susceptible to fungal infections

• Thrombocytopenia
• Bleeding - purpura, petechiae

Complications of treatment

• N+V

• Hair loss

• Liver, renal dysfunction

• Tumour lysis syndrome (during first course of treatment)

• Infection
• Bacterial: empirical treatment with broad spectrum antibiotics (particularly covering gram negatives) as soon as neutropenic fever
• Fungal - if prolonged neutropenia and persisting fever unresponsive to anti-bacterial agents
• Protozoal e.g. PJP

• Late effects e.g. loss of fertility, cardiomyopathy with anthracyclines