A 14-year-old boy presented to his General Practitioner (GP) with a 2-week history of a dry cough. This was worse on exertion. He was treated with inhaled bronchodilators. The symptoms did not improve. Ten days later he returned to the GP complaining of fevers, tiredness and a skin rash. On examination he appeared pale and unwell, had a fever of 37.8°C, purpura on the feet and ankles and mild hepatosplenomegaly. He was referred to hospital. Chest X-ray revealed a widened superior mediastinum and a small right-sided pleural effusion. Full blood count was abnormal: haemoglobin 10.2 g/dl, white blood cell (WBC) count 73 × 109/l, neutrophils 0.8 × 109/l, platelets 23 × 109/l. The peripheral blood film revealed a monomorphic population of lymphoblasts and associated neutropenia and thrombocytopenia. Bone marrow aspirate confirmed the suspicion of acute lymphoblastic leukaemia (ALL) (Figure 17.1). Immunophenotyping confirmed T-cell ALL.
What is the current approach to management of this condition?
What factors affect prognosis?
Bone marrow in acute lymphoblastic leukaemia.
Acute lymphoblastic leukaemia is the commonest childhood malignancy, accounting for 35% of cases; 400–500 cases of ALL are diagnosed in children per year in the UK.1 There is a peak in incidence between the ages of 2 and 5 years. Children present with bone marrow failure (anaemia, neutropenia and thrombocytopenia) due to the proliferation of abnormal lymphoid cells (blasts) in the bone marrow. T-cell immunophenotype is associated with chest disease, which may present with large mediastinal lymphadenopathy often with pleural effusion. Occasionally this may be associated with superior vena cava obstruction.
It has long been thought that there is an association between infection (as a second event) and the development of ALL in individuals with a predisposition to develop ALL, known as the Greaves hypothesis.2 There is now molecular evidence that this is initiated in utero.3,4 It is postulated that there is an abnormality/dysregulation of the immune system such that in individuals destined to develop ALL, an exposure to an otherwise innocuous infection in early childhood stimulates an extreme response in the form of immature lymphoid cells, i.e. lymphoblasts (ALL). A recent publication5 has shown that there is an increase in the number of infections in very early childhood (including the neonatal period) in children who later develop ALL, compared with controls, suggesting an underlying abnormality of the immune system.
Immunophenotyping of lymphoblasts at diagnosis categorizes patients into ALL of B- or T-cell lineage by virtue of CD protein expression.
Good risk features include age <10 years, low WBC count at diagnosis (<50 × 109/l), CD10 expression (common ALL antigen), t(12;21) translocation (TEL/AML1) molecular cytogenetic abnormality, high hyperdiploidy and rapid early response to therapy (<25% bone marrow blasts at day 15 of therapy).
Poor-risk features include age ...