Acute Lymphoblastic Leukaemia

Overview

Acute lymphoblastic leukaemia (ALL) is a cancer of the lymphoid cell line leading to large numbers of immature lymphoid progenitors (lymphoblasts) emerging from the bone marrow and entering the circulation.

Normal lymphoblasts develop into mature lymphocytes (B- or T-cells), however, malignant lymphoblasts gain mutations that promote abnormal proliferation. The excessive proliferation of lymphoblasts interferes with the production of new red blood cells, white blood cells, and platelets, giving rise to the signs and symptoms seen.

Epidemiology

• ALL is the most common cancer in children
• Males are affected more than females
• Most common in children <5 years

Risk Factors

• Age <5 years
• Male sex
• Family history
• Previous chemotherapy
• Exposure to radiation and smoking
• Down’s syndrome

Example History

A 4-year-old girl has lethargy, dyspnoea, and unexplained bruising. On examination, she is pale and has hepatosplenomegaly.

Investigations:

Presentation

The excessive proliferation of lymphoblasts interferes with the production of new red blood cells, white blood cells, and platelets, giving rise to:

• Features of anaemia:
  • Pallor
  • Fatigue
  • Dyspnoea
  • Palpitations
• Features of thrombocytopenia:
  • Bruising/petechiae
  • Epistaxis
• Features of neutropenia:
  • Frequent and/or severe infections
  • Fever – either a constitutional symptom or due to infection 
• Other features are due to lymphoblast infiltration and spreading to other sites such as:
  • Bones, causing bone pain
  • Splenomegaly with or without hepatomegaly
    • Splenomegaly occurs due to increased cell sequestration which can lead to hepatomegaly
    • Both can also be due to infiltration
  • Lymph nodes, causing lymphadenopathy
  • The testicles, often causing painless unilateral testicular enlargement

Differential Diagnoses

Acute myeloid leukaemia (AML)

• Both can present very similarly
• Blood films show Auer rods in AML
• Blood films show promyelocytes with bilobed nuclei

Immune thrombocytopenia

• Full blood count only shows thrombocytopenia
• Blood films show no abnormal leukocytes (i.e. no blast cells)
• Bone marrow aspiration and biopsy are normal

Chronic myeloid leukaemia

• Blood film shows maturing or mature myeloid cells i.e. they are in different stages of maturation
• Splenomegaly is more profound and can cause abdominal discomfort

Investigations

All patients

• Full blood count (FBC) and white cell differential:
  • Normocytic normochromic anaemia
  • Leukocytosis
  • Neutropaenia
  • Thrombocytopenia may be present
• Blood film:
  • Lymphoblasts seen – not sufficient enough to diagnose ALL
• Coagulation profile:
  • This is generally done in patients with bleeding and petechiae to screen for coagulopathy
• Urea and electrolytes (U&Es):
  • Hypercalcaemia may be seen – due to bone infiltration/PTH-like hormone release
  • Hyperphosphataemia may be seen – due to leukaemia itself or tumour lysis
  • Hyperkalaemia – due to leukaemia cell lysis
  • Hyperuricaemia – due to tumour lysis
• Liver function tests (LFTs):
  • May be deranged if there is liver infiltration
• Lactate dehydrogenase (LDH):
  • May be elevated due to increased cell turnover
• Immunophenotyping:
  • Involves using flow cytometry on blood and/or bone marrow blood samples
  • Identifies specific protein markers on cells which correlate their lineage (e.g. CD20 is a protein found on B-cells)
• Bone marrow aspiration + trephine biopsy:
  • ≥20% lymphoblasts in the bone marrow is diagnostic for ALL

Management

Overview

Leukaemia is generally treated using chemotherapy, steroids, radiotherapy, surgery and bone marrow transplantation.

Complications

• Pancytopenia
• Neutropenic sepsis
• Haemorrhage
• Anaemia

Prognosis

• The prognosis is worse in adults
• Factors associated with a worse prognosis are:
  • <12 months or ≥10 years
  • White cell count ≥50 x 10⁹/L
  • Male sex