Oncology - Leukaemia

Question 1

Definition

Answer 1

Acute lymphoblastic leukaemia = proliferation of lymphoblasts, most commonly of the B cell lineage.
- MC cancer in children and associated with Down Syndrome
- t(12;21) MC cytogenic abnormality in children

Question 2

Epidemiology

Answer 2

• Bimodal age distribution: 4-5 years and 50 +
• Previous chemotherapy
• Radiation exposure
• Down syndrome: X 20
• Benzene exposure: painters, petroleum, rubber, manufacturers
• Family history

Question 3

Pathophysiology

Answer 3

Genetic aberrations result in the excessive proliferation of lymphoblasts which accumulate in the bone marrow leading to bone marrow failure, with subsequent anaemia and thrombocytopenia . Lymphoblasts ‘leak’ into the blood and can invade a number of tissues, including the testicles, meninges, and kidneys.

Question 4

Signs

Answer 4

• Lymphadenopathy
• Hepatosplenomegaly
• Pallor
• Flow murmur due to anaemia
• Parotid infiltration
• Testicular swelling: due to testicular involvement
• Central nervous system (CNS) involvement e.g. meningism, and cranial nerve palsy

Question 5

Symptoms

Answer 5

• Fatigue
• Loss of appetite
• Easy bruising, prolonged bleeding and mucosal bleeding: due to thrombocytopaenia
• Bone pain: due to bone marrow infiltration
• Weight loss
• Recurrent infections: due to neutropaenia
• Fever: present in half of patients

Question 6

Treatment

Answer 6

Pre-phase: 5 - 7 days of treatment shortly after diagnosis
- Treat with corticosteroids +/- additional chemotherapy agent

Induction: 4 - 8 week therapy to induce remission, defined as < 5% blast cells in bone marrow
- e.g. corticosteroids , vincristine or doxorubicin (chemotherapy)
- + Imatinib if Philadelphia chromosome-positive
- Intrathecal therapy if there is CNS involvement

Consolidation: Up to 1 year of high-dose chemotherapy , which is started after complete remission
- The aim of treatment is to eliminate clinically undetectable residual leukaemia, hence preventing relapse

Maintenance:
- 2 years of mercaptopurine and methotrexate therapy
- The aim of treatment is to eliminate minimal residual disease (leukemic cells not present on microscopy but cell surface markers still present)

Question 7

Treatment Second Line

Answer 7

Bone marrow transplantation: may be used as consolidation therapy in people at high risk of relapse, or for treating relapse when it occurs

Question 8

Complications

Answer 8

2’ to chemo:
- Myelosuppression and neutropaenic sepsis
- Tumour lysis syndrome
2’ to ALL
- Myelosupression and neutropaenic sepsis
- Extramedullary involvement: CNS, testicular and renal involvement
- Infertility: due to lymphoblastic invasion