43  Leukaemia

Leukaemia is the most common childhood malignancy, representing about one-third of all cancers diagnosed in children. It is a malignant disorder of the blood and bone marrow characterised by uncontrolled proliferation of abnormal white blood cells. These immature cells crowd the marrow, impairing the production of normal blood cells and leading to anaemia, thrombocytopenia, and neutropenia. For medical students, understanding leukaemia requires an integrated view of its epidemiology, aetiology, pathophysiology, clinical presentation, diagnosis, treatment, and outcomes.

43.1 Introduction

Leukaemia in children is a heterogeneous group of disorders arising from the malignant transformation of haematopoietic precursor cells. It is broadly divided into acute lymphoblastic leukaemia (ALL), the most common type, and acute myeloid leukaemia (AML). Chronic leukaemias are rare in childhood. The disease disrupts normal bone marrow function and causes systemic manifestations due to infiltration of organs by leukaemic cells.

43.2 Incidence and Prevalence

• Childhood leukaemia accounts for approximately 25–35% of all paediatric cancers.
• The global incidence is about 3–4 per 100,000 children per year.
• ALL is more common than AML, with a peak incidence between ages 2 and 5 years.
• There is a slight male predominance and variation across ethnicities, with higher rates in high-income countries.
• Improvements in treatment have markedly increased survival, with 5-year survival rates for ALL exceeding 80% in developed settings.

43.3 Aetiology

The exact cause of leukaemia remains unclear, but multiple interacting factors have been implicated:

• Genetic predisposition:
  • Children with syndromes such as Down syndrome, Li-Fraumeni syndrome, and Fanconi anaemia are at higher risk.
• Chromosomal abnormalities: Translocations such as t(12;21) in ALL or t(8;21) in AML are common.
• Environmental factors: Ionising radiation, certain chemotherapeutic agents, and exposure to benzene.
• Infections and immune dysregulation: Delayed immune development and abnormal immune responses to infections have been proposed.
• Familial risk: Having a sibling with leukaemia increases the risk modestly.

43.4 Pathophysiology

Leukaemia results from genetic mutations in haematopoietic stem or progenitor cells leading to:

1. Uncontrolled proliferation of abnormal blasts.
2. Failure of differentiation, with accumulation of immature cells.
3. Bone marrow failure, causing:
   • Anaemia → fatigue, pallor.
   • Neutropenia → infections.
   • Thrombocytopenia → bleeding.
4. Tissue infiltration by leukaemic cells:
   • Hepatosplenomegaly.
   • Lymphadenopathy.
   • CNS involvement (headache, vomiting, cranial nerve palsies).
   • Bone pain from marrow expansion.

43.5 Signs and Symptoms

Children typically present with non-specific symptoms, making early recognition challenging.

• General symptoms: Fatigue, fever, anorexia, weight loss.
• Bone marrow failure manifestations:
  • Pallor, tachycardia, and lethargy from anaemia.
  • Easy bruising, petechiae, and mucosal bleeding from thrombocytopenia.
  • Recurrent infections due to neutropenia.
• Organ infiltration:
  • Lymphadenopathy, hepatomegaly, splenomegaly.
  • Bone or joint pain, limp.
  • CNS signs: vomiting, seizures, headaches.
  • Testicular enlargement (especially in ALL).

43.6 Differential Diagnosis

Conditions that mimic leukaemia include:

• Aplastic anaemia.
• Infectious causes: EBV, HIV, tuberculosis.
• Other malignancies: Lymphomas, neuroblastoma.
• Rheumatological disorders: Juvenile idiopathic arthritis.
• Storage disorders with hepatosplenomegaly.

43.7 Investigations

Workup includes both laboratory and imaging studies:

• Initial tests:
  • Full blood count (FBC) often shows anaemia, thrombocytopenia, leukocytosis or leukopenia.
  • Blood film reveals circulating blasts.
• Confirmatory tests:
  • Bone marrow aspiration and biopsy showing >25% blasts.
  • Flow cytometry for immunophenotyping (B-cell vs T-cell ALL, AML subtypes).
• Cytogenetics and molecular studies: Prognostic significance (e.g., t(9;22) Philadelphia chromosome).
• Additional workup:
  • Lumbar puncture for CNS involvement.
  • Chest X-ray to check for mediastinal mass.
  • Biochemistry: uric acid, LDH, renal and liver function.

43.8 Treatment

Management of leukaemia is complex and requires a multidisciplinary team. It can be categorised into stages:

43.8.1 Emergency Management (at presentation)

• Stabilisation: Manage anaemia, thrombocytopenia, and infections.
• Blood product support: Packed RBCs, platelets.
• Treatment of tumour lysis syndrome: Hydration, allopurinol or rasburicase.
• Empirical antibiotics for febrile neutropenia.

43.8.2 Ongoing Management (definitive therapy)

• Chemotherapy is the backbone of treatment:
  • Induction → achieve remission.
  • Consolidation/intensification → eradicate residual disease.
  • Maintenance → prevent relapse.
• CNS prophylaxis with intrathecal methotrexate.
• AML requires more intensive regimens.
• Targeted therapies (e.g., tyrosine kinase inhibitors for BCR-ABL positive ALL).

43.8.3 3. Preparation for Discharge

• Education of caregivers about infection prevention, medication adherence, and follow-up.
• Arrangements for outpatient chemotherapy and monitoring.
• Psychosocial support for the child and family.

43.8.4 4. Long-Term Management

• Monitoring for relapse with clinical exam and minimal residual disease testing.
• Managing late effects of chemotherapy: growth retardation, infertility, cardiotoxicity.
• Vaccinations and infection prophylaxis.
• Consideration of stem cell transplant in high-risk or relapsed cases.

43.9 Complications

• Early: Tumour lysis syndrome, febrile neutropenia, bleeding, sepsis.
• During therapy: Chemotherapy toxicity (mucositis, hepatotoxicity, cardiotoxicity).
• Late: Relapse, secondary malignancies, growth and endocrine abnormalities, learning difficulties.

43.10 Prevention

• Currently, there are no definitive preventive strategies for most cases.
• Avoidance of unnecessary radiation and known chemical carcinogens is recommended.
• Genetic counselling for families with hereditary cancer syndromes.

43.11 Prognosis

• Prognosis depends on age, initial white cell count, cytogenetic abnormalities, and response to therapy.
• ALL: 5-year survival >80% in developed countries, lower in resource-limited settings.
• AML: Lower survival (~60%), requires more intensive therapy.
• Relapse remains a major challenge, with outcomes poorer after recurrence.

43.12 Conclusion

Childhood leukaemia, though the most common paediatric cancer, is a highly treatable condition with modern chemotherapy protocols. A good understanding of its presentation, investigations, and treatment approach is essential for practitioners, particularly in Ghana, where delayed diagnosis and limited resources pose challenges. With early recognition, appropriate supportive care, and treatment adherence, survival rates continue to improve globally.