Malignant disease affects about 1 in 600 people during childhood (1 per 10 000 children per year). The commonest malignancies are acute leukaemia and central nervous system (CNS) tumours. Overall, there has been a significant improvement in prognosis over recent years due to the use of well-researched and standardized chemotherapy regimes delivered in specialized paediatric oncology centres. The prognosis still depends largely on the particular type of malignancy and on the progression of the disease at the time of diagnosis.

Acute Leukaemia

Leukaemia is the most common malignancy in childhood (30%) with an annual incidence of 3 per 100 000 children. It is due to the malignant proliferation of white cell precursors within the bone marrow. These ‘blast’ cells escape into the circulation and may be deposited in lymphoid or other tissue. The commonest type of leukaemia in childhood is acute lymphoblastic leukaemia (ALL), where the blast cells are precursors of lymphocytes. Chronic leukaemias are very rare in childhood.

ALL can occur at any age, but the peak is between 2 and 5 years. The prognosis is worse for those presenting under the age of 2 or over 10 years old. The onset may be insidious with malaise, anorexia and then pallor, bruising or bleeding. Lymphadenopathy and splenomegaly may be present, and bone pain may occur. Peripheral blood usually, but not always, shows anaemia, thrombocytopenia and a raised white cell count. Those with an extremely high white cell count (>50 × 10⁹/L) carry a worse prognosis. Blast cells may be seen on the peripheral blood film. The diagnosis is confirmed by a bone marrow aspirate, which shows the marrow infiltrated with blast cells. Cells are examined by immunophenotyping and cytogenetic analysis as these give important prognostic information. In more than 90% of cases specific genetic abnormalities can be seen in the leukaemic cell line. There may be increased numbers of chromosomes or translocations: for example, the t12:21 translocation creates a TEL-AML1 fusion gene in 20% of children with ALL. Acute lymphoblastic leukaemia can be subdivided into common (75%), T-cell (15%), null (10%) and B-cell (1%).

Treatment of ALL involves chemotherapy to induce remission (i.e. remove all blast cells from the circulation and restoration of normal marrow function). Complete remission is induced in 95% of children. Intensification chemotherapy maintains remission, and methotrexate or cranial irradiation protects the CNS from involvement. Monthly cycles of maintenance chemotherapy are then required. Children who relapse are often offered high-dose chemotherapy and bone marrow transplantation. The overall prognosis for acute leukaemia is good, with up to 80% survival.

Short-Term Side Effects of Treatment

Tumour Lysis Syndrome

The breakdown of large numbers of malignant cells either before or during treatment can lead to very high serum urate, phosphate and potassium levels. Urate crystals can precipitate in the kidneys causing renal failure. Tumour lysis syndrome can be prevented by good hydration and the use of allopurinol (a xanthine oxidase inhibitor) or uric acid oxidase.

Bone Marrow Suppression and Febrile Neutropenia

Bone marrow suppression may be due to invasion by tumour cells or the effect of chemotherapy. Anaemia and thrombocytopenia can be treated with infusions of red cells and platelets. Neutropenia (neutrophil count <1.0 × 10⁹) is difficult to treat and means the patient is at risk of serious infection. Consequently any significant fever or signs and symptoms of infection while neutropenic should be investigated and treated aggressively with broad-spectrum antibiotics until culture results are known.

Immunosuppression

Severe immunosuppression may result from treatment. This leaves the child at risk from normally trivial infections. Patients should not be given live vaccines and if exposed to varicella (chickenpox) they should be given specific immunoglobulin. If the patient goes on to develop chickenpox they should be treated with aciclovir and immunoglobulin.

Nutrition

Inflammation and disruption of gut mucosa and mouth ulcers as well as anorexia can lead to poor calorie intake. Nutritional support with food supplements may be necessary.

Late Sequelae of Treatment

Short stature or asymmetrical growth may be caused by radiotherapy to the spine or hypothalamo-pituitary axis. The latter may also cause delayed puberty and other endocrine dysfunction including growth hormone deficiency, hypothyroidism, cortisol deficiency and gonadal failure. Cranial irradiation, especially in very young children, can lead to neurocognitive effects such as memory loss and poor attention and for this reason intensive chemotherapy and intrathecal treatment is used in some centres as an alternative. Chemotherapy can lead to subfertility, nephrotoxicity, deafness, pulmonary fibrosis and cardiomyopathy. There is a significant risk (about 12%) of second cancers due to the carcinogenic effect of chemo- and radiotherapy and an increased genetic tendency. Chronic ill health and poor school attendance may have long-term effects on educational achievement, although this may be minimized by good liaison with school and specialist staff.