A three-year-old boy presents to the GP with a rash. His mother mentions that he bruises easily and two weeks earlier he had a viral illness. Examination reveals cervical lymphadenopathy in keeping with a recent URTI. Chest and abdominal examination is unremarkable. A petechial rash and fairly extensive bruising of all limbs is noted.
The GP immediately arranges an FBC and the results are telephoned to the surgery later that day:
- Haemoglobin: 11.3g/dl
- White cell count: 3.4 x 109/l
- Lymphocyte count: 1.9 x 109/l
- Neutrophils: 1.1 x 109/l
- Platelets: 6 x 109/l
- Blood film: reactive lymphocytes.
The child is referred urgently to hospital where a diagnosis of immune thrombocytopenic pupura is made. As he is otherwise asymptomatic he is discharged with lifestyle advice and a follow-up in two weeks.
The child becomes unwell 12 days later – drowsy with a temperature of 38.5°C – and his mother takes him to A&E. He is pyrexial, hypotensive and peripherally shut down, with a Glasgow coma score of 13/15. Bloods are taken, and fluid resuscitation and broad-spectrum antibiotics started. Urgent CT excludes an intracranial bleed. Septic shock is diagnosed and bloods reveal severe neutropenia with occasional blasts seen on the film. He is transferred to the high-dependency unit for inotropic support, fluid resuscitation and platelet transfusion. Chest X-ray reveals left basal consolidation. Ultrasound reveals splenomegaly. Blood cultures grow gram-negative bacilli. B-cell acute lympho-blastic leukaemia (ALL) is confirmed on bone marrow aspirate. Treatment is initiated and he moves into remission.
The problem
Acute lymphoblastic leukaemia (ALL) is the most common malignancy in childhood, with 400 cases per year in the UK. The peak age for ALL is between two and four years. Overall five-year survival rates are 85%. Favourable prognostic features include:
- Age between one and 10 years
- White blood cell count at presentation <50 x 109/l and good risk cytogenetics.
Early mortality at diagnosis is rare, but still occurs. Understandably this is very distressing for all involved as the condition is curable in most cases.
This case highlights how quickly a child can become unwell with life-threatening complications at the onset of disease and how important it is to monitor frequently in the first few weeks of any significant abnormality in the blood count.
Features
The most common presenting feature of ALL is general lethargy. Other symptoms include:
- Recurrent fever
- Pallor
- Bruising/petechial rash
- Mucosal bleeding
- Cervical lymphadenopathy
- Abdominal pain
- Reduced appetite
- Bone pain because of bone marrow expansion – typically hips and thighs, but also sternum or back
- Joint pains
- Headaches
- Breathlessness
- Rashes (rare presentation).
Management
If a child presents to the GP with any symptoms that raise the possibility of acute leukaemia, arrange an urgent FBC and review results the same day.
- If FBC is abnormal, discuss with haematologist on call; if ALL is suspected, urgent review in hospital is required.
- If FBC is normal with a clinical suspicion of malignancy, then urgent two-week referral is warranted or, if the child is unwell, arrange urgent admission as a normal FBC does not exclude acute leukaemia.
- If FBC reveals an isolated cytopenia, monitor low haemoglobin, white count or platelet count frequently in the initial period to ensure it is stable or resolves because leukaemia can present with isolated cytopenias before a child becomes truly pancytopenic or before blasts appear in the film.
Other important actions that would be taken in hospital include:
- Haemorrhage prevention – transfuse platelets to safe level.
- Treatment for possible sepsis – fever is often due to underlying disease but patients can present with sepsis and deteriorate quickly.
- Intravenous hydration.
Treatment is with intensive chemotherapy via a Hickman line in addition to oral steroids and intrathecal chemotherapy for four to six months, followed by 18–24 months of maintenance treatment. This is predominantly oral chemotherapy with monthly IV vincristine and steroid pulses and three-monthly intrathecal chemotherapy to prevent central nervous system relapse. Most treatment is done in day care and outpatients, and children will be encouraged to attend nursery or school when well, even if they are neutropenic.
Annual flu vaccination is required for patients and their immediate family. Re-immunisation is necessary six months after completion of maintenance chemotherapy. No other immunisations should be given while they are on treatment.
Side effects of chemotherapy are numerous, and common complications include infections, central-line complications, thrombosis, bleeding, peripheral neuropathy, bone infarcts and osteoporosis because of steroids (in older children and teenagers). Patients may also experience longer-term issues, including reduced fertility, reduced growth, delayed puberty, damage to heart, bones or peripheral nervous system. The educational, social and psychological impact of the diagnosis and treatment on the patient and their family can also be profound and requires appropriate support.
Relapse is most common within the first two years of treatment completion but can occur many years later.
Dr Helen Campbell is a paediatric haematology consultant at Alder Hey Children’s Hospital, Liverpool
Alder Hey is one of Europe’s busiest children’s hospitals providing care for over 275,000 patients each year. Alder Hey has a broad range of hospital and community services for direct referral from primary care. It is the designated national centre for head and face surgery and a Centre of Excellence for children with cancer, spinal and brain disease. Alder Hey has been chosen to be a national centre for heart surgery, a respiratory ECMO surgery centre and one of just four specialist centres to provide surgery for drug-resistant epilepsy. For more information go to: alderhey.nhs.uk
