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 features

• Marrow failure - anaemia, infections, bleeding
• Leukaemic effects - high count with obstruction of circulation, involvement of areas outside the marrow and blood (extra-medullary) e.g. CNS, testis
• Bone pain

Investigations

• Bloods:
  • 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