ACHES AND PAINS
History
Hannah is a 5-year-old girl seen in the paediatric day unit at the request of the GP. Hannah has been seen several times in the past few weeks with non-specific symptoms. Initially she was just off-colour and lacking in energy, wanting to sit and watch television rather than play outside. She was complaining that her legs were aching and she needed regular doses of paracetamol. The GP and her parents thought this might all be related to her recently starting full-time school and her mother went in to talk to the staff, worried about possible bullying. Hannah then had an ear infection with a high temperature that was slow to respond to antibiotics and was therefore assumed to be viral. Her admission has been precipitated this week because she has started to refuse to walk, complaining that ‘she hurts all over’. The GP requested a full blood count (FBC) and erythrocyte sedimentation rate (ESR) and has been phoned with the results below.
Examination
Hannah is quiet and pale. She is sitting on her mother’s knee and is reluctant to be examined, crying when she is moved. Her temperature is 37.8C. She has widespread lymphadenopathy, including supraclavicular. She is clinically anaemic but not jaundiced. She has bruises on her shins, left thigh and right upper arm. Her pulse is 96 beats/ min and heart sounds are normal, but she has a grade 2 systolic murmur located at the left sternal edge. Her chest is clear. In the abdomen there is 4 cm hepatomegaly and her spleen is palpable 2 cm below the left costal margin. Her left ear drum is dull and pink but the right is normal, as is her throat. Although she resists movement of her joints, there is no obvious swelling, deformity or overlying skin change.
INVESTIGATIONS
Normal
Haemoglobin 7.3 g/dL 11.5–15.5 g/dL
White cell count 3.4 109/L 5.5–15.5 109/L
Neutrophils 1.3 109/L 3.0–5.8 109/L
Lymphocytes 1.8 109/L 1.5–3.0 109/L
Platelets 36 109/L 150–400 109/L
ESR 88 mm/hour 0–10 mm/hour
Blood film Atypical lymphocytes seen
Questions
• What is the most likely diagnosis?
• How can it be confirmed?
• Outline the treatment of this condition
• What factors are associated with a poor prognosis?
Medicine
Hannah’s blood count shows pancytopenia, which is due to either bone marrow (BM) infiltration or failure (see Case 48, A pale child, p. 143). She has the clinical symptoms and signs of infiltration – the bone pain is due to marrow expansion. Children may not localize the pain, and generalized non-specific symptoms culminating in a reluctance to move and weight-bear are common. There may be bone tenderness. Hannah has evidence of extramedullary involvement with hepatosplenomegaly and lymphadenopathy. Supraclavicular nodes are always suspicious. Bruises below the knees are very common in children, but those at sites other than the shins may be pathological. The murmur is almost certainly a flow murmur due to anaemia. The most likely diagnosis is acute leukaemia, probably lymphoblastic (ALL) because this accounts for 80 per cent of leukaemias in childhood. Leukaemic ‘blast’ cells may not be observed on a routine peripheral blood film examination or may be misinterpreted. The peripheral FBC may even be normal, causing diagnostic difficulty in differentiating it from conditions that present with similar features, e.g. infectious mononucleosis or rheumatoid arthritis. Analysis of a BM aspirate is essential. This differentiates ALL from acute myeloid leukaemia (AML) and other malignant causes of BM infiltration, such as neuroblastoma. It also enables classification of ALL using cell membrane markers and cytogenetic and molecular genetic features which influence treatment decisions and prognosis. Current treatment for ALL is in four phases:
1. Remission induction. Four weeks of combination chemotherapy. More than 95 per cent show BM remission by day 28.
2. Consolidation and CNS protection. Oral chemotherapy is commenced. Cytotoxic drugs penetrate poorly into the CNS. A course of weekly intrathecal (IT) drugs is given to prevent later CNS relapse. IT drugs are also given during induction and throughout maintenance.
3. Delayed intensification(s). Remission at day 28 is often only apparent. One or two courses (depending on risk) of intense chemotherapy are dovetailed with blocks of maintenance chemotherapy.
4. Continuing maintenance. Chemotherapy continues for a total of 2 years in girls and 3 years in boys. Patients are immunosuppressed and at risk of opportunistic infections. Co-trimoxazole is given to prevent Pneumocystis carinii pneumonia.
Poor prognostic factors in acute lymphoblastic leukaemia
• Total white cell count 100 109 /L at presentation
• Outside age range 2–10 years
• Male sex
• T-cell (15 per cent) or mature B-cell (1 per cent) origin (Common-ALL (85 per cent) from B-cell progenitors has best prognosis)
• Certain chromosome abnormalities – hypodiploidy, presence of Philadelphia chromosome (Others, e.g. hyperdiploidy, confer a favourable prognosis) • CNS disease at presentation
• Slow response to treatment, 5% blasts persisting on day 28 BM
Overall prognosis for ALL is excellent with a 5-year survival 80 per cent
KEY POINTS
• Acute leukaemia can present with very non-specific and indolent clinical features.
• A bone marrow aspirate is essential to confirm or refute a diagnosis of acute leukaemia.
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