Leukaemia in Children

Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management | References

Definition

Leukaemia is a type of blood cancer that affects the bone marrow and blood, leading to the uncontrolled production of abnormal white blood cells. It is the most common cancer in children, and there are two main types: Acute Lymphoblastic Leukaemia (ALL) and Acute Myeloid Leukaemia (AML). ALL accounts for approximately 80% of childhood leukaemia cases, while AML is less common. Both types lead to a reduced number of normal blood cells, causing anaemia, increased infection risk, and bleeding disorders.

Aetiology

The exact cause of leukaemia in children is not fully understood, but several factors may contribute:

• Genetic predisposition: Certain genetic syndromes, such as Down's syndrome, increase the risk of developing leukaemia.
• Radiation exposure: Previous exposure to high doses of radiation, either from medical treatments or environmental sources, increases the risk.
• Chemotherapy: Children treated with chemotherapy for other cancers may have an increased risk of developing secondary leukaemia.
• Viral infections: In rare cases, infections like the Epstein-Barr virus (EBV) have been linked to leukaemia.
• Family history: A family history of leukaemia may slightly increase the risk.

Pathophysiology

Leukaemia originates in the bone marrow, where blood cells are produced. In children with leukaemia, the bone marrow produces a large number of immature, abnormal white blood cells (blasts). These abnormal cells crowd out the normal blood cells, leading to a reduction in red blood cells (causing anaemia), platelets (causing bleeding disorders), and healthy white blood cells (increasing the risk of infection). The abnormal cells can also spread to other parts of the body, including the liver, spleen, and central nervous system, causing further complications.

Risk Factors

• Genetic disorders: Children with Down's syndrome, Fanconi anaemia, or Bloom syndrome have an increased risk of developing leukaemia.
• Radiation exposure: Exposure to high levels of radiation, especially in utero or during early childhood.
• Previous chemotherapy: Treatment with certain chemotherapy agents can increase the risk of developing secondary leukaemia.
• Family history: Having a sibling or close relative with leukaemia can slightly increase the risk.
• Immune system disorders: Certain inherited immune system disorders, such as ataxia-telangiectasia, may increase leukaemia risk.

Signs and Symptoms

The signs and symptoms of leukaemia in children can vary depending on the type and extent of the disease but typically include:

• Anaemia: Fatigue, pallor, and shortness of breath due to a reduced number of red blood cells.
• Frequent infections: Due to a lack of functional white blood cells, children may experience recurrent or severe infections.
• Bruising and bleeding: Easy bruising, nosebleeds, or prolonged bleeding from minor cuts, due to a low platelet count.
• Bone and joint pain: Leukemic cells may accumulate in the bone marrow, causing pain in bones or joints.
• Swollen lymph nodes: Painless swelling of lymph nodes, particularly in the neck, underarm, or groin.
• Enlarged liver or spleen: Abdominal swelling or discomfort due to the accumulation of abnormal cells in the liver or spleen.
• Fever: Persistent low-grade fevers without any obvious infection.
• Weight loss: Unexplained weight loss or lack of appetite.

Investigations

Diagnosis of leukaemia involves a series of tests to confirm the presence of abnormal blood cells and determine the type of leukaemia:

• Full blood count (FBC): A blood test will show abnormal white blood cell counts, low red blood cells, and low platelets.
• Bone marrow biopsy: A sample of bone marrow is examined to look for the presence of leukaemia cells.
• Flow cytometry: Used to analyse the type and maturity of blood cells and to classify the leukaemia as ALL or AML.
• Genetic testing: To identify specific genetic mutations associated with different types of leukaemia.
• Lumbar puncture: To check if the leukaemia has spread to the central nervous system (CNS).
• Imaging: Chest X-ray or CT scan may be used to detect enlarged lymph nodes or other signs of the disease.

Management

The treatment of leukaemia in children depends on the type and stage of the disease. The main treatments include:

Chemotherapy:

• Most children with leukaemia are treated with chemotherapy, which uses drugs to kill cancer cells or stop them from growing. The treatment is usually delivered in cycles and can be given orally, intravenously, or directly into the spinal fluid (intrathecal chemotherapy).

Radiation Therapy:

• Radiation may be used in certain cases, especially if the cancer has spread to the brain or spinal cord. It is more commonly used in AML than in ALL.

Targeted Therapy:

• Some children with specific genetic mutations may benefit from targeted therapies, which focus on blocking the action of specific proteins involved in cancer cell growth.

Bone Marrow Transplant (Stem Cell Transplant):

• In some cases, particularly for children with high-risk leukaemia or those who relapse, a bone marrow or stem cell transplant may be considered. This involves replacing the diseased bone marrow with healthy donor cells.

Supportive Care:

• Supportive care, including blood transfusions, antibiotics, and antifungal medications, is critical for managing the side effects of treatment and preventing infections.
• Pain management and psychological support are also essential for the child's overall well-being.

Referral:

• 2-week wait (2WW) referral: Any child presenting with persistent fatigue, pallor, recurrent infections, unexplained bruising, or lymphadenopathy should be urgently referred for specialist evaluation and blood tests under the 2-week wait cancer referral pathway.
• Children with leukaemia should be managed by a paediatric oncologist and a multidisciplinary team for optimal care.

References

1. NICE (2024). Leukaemia in Children: Diagnosis and Management Guidelines. Available at: NICE Guidance
2. Cancer Research UK (2023). Leukaemia in Children Overview. Available at: Cancer Research UK
3. British Medical Journal (2023). Management of Paediatric Leukaemia. Available at: BMJ