L11: Malignant blood disorders

Question 1

Types of blood and bone marrow cancers

Answer 1

1. Leukaemias
2. Myeloproliferative neoplasms (e.g. polycythaemia vera - high Hb, enlarged spleen)
3. Lymphomas (e.g. Hodgkin or non-Hodgkin)
4. Myeloma (cancer of plasma cells)

Question 2

Leukaemia

Answer 2

• Proliferation of immature bone marrow cells
• Expand and replace normal bone marrow cells
• Can arise from myeloid or lymphoid lineage (i.e. acute myeloid leukaemia or acute lymphoblastic leukaemia)
• Can be acute or chronic

Question 3

Pathogenesis of leukaemia

Answer 3

• Congenital or inherited risk factors (e.g. down syndrome or inherited abnormality of immune system)
• Viral infections (retrovirus associated with rare T cell leukaemia)
• Radiation* (could be therapeutic - 5% of patients)
• Chemical/DNA damaging drugs*
• most common

Most cases = cannot identify and environmental or congenital risk factor

But cytogenetic and molecular changes (acquired somatic) found in most leukaemias (impt in prognosis, therapy)

Question 4

Philadelphia chromosome

Answer 4

• t(9;22) = translocation between 9 & 22
• Found in all CML, 20% of adults with acute leukaemia
• Gives fusion gene then fusion protein BCR-A BL –> proliferation of myeloid cells
• Poor prognosis (usually transplant req)
• Target for novel drug: Imatinib (tyrosine kinase inhibitor)
• Imatinib standard of care for CML (survival increase)

Question 5

Acute leukaemias

Answer 5

Occurs in all ages

• ALL (acute lymphoblastic leukaemia) predominantly in childhood (85%)
• AML (acute myeloid leukaemia) predominantly adults (85%)
• Overall 2-3 cases per 100,000 per year

Question 6

Acute leukaemia clinical presentation

Answer 6

Clinical presentation due to BM failure:

• Anaemia = fatigue, dyspnoea, chest pain
• Neutropenia = infection, slow healing wound
• Thrombocytopenia = (low platelets) bruising and bleeding (petechiae, purpura, haemorrhage in mucosa of mouth)

Other signs and symptoms due to organ infiltration:

• Bone pain
• Enlarged liver, spleen, lymph nodes
• Other sites e.g. gum hypertrophy

Question 7

Leukaemia on FBC

Answer 7

• Low Hb/anaemia
• WBCs increase: due to circulating blasts (leukaemia cells)
• Neutrophils low
• Severe thrombocytopenia often <20

Question 8

Diagnosis of leukaemia

Answer 8

Bone marrow biopsy:
- Aspirate (fluid from BM space)
- Trephine (core biopsy)
- Morphology of BM: >20% blasts 
Specialised testing:
- Immunophenotype (AML or ALL)
- Chromosomes (e.g. philadelphia, give indication of prognosis)
- Molecular studies

Question 9

Acute leukaemia general and supportive care

Answer 9

• Intensive transfusion support: red cells, platelets
• Management of infection
• Tunnelled line for vascular access
• Patient and family support

Question 10

Chemotherapy for acute leukaemia

Answer 10

• Induction therapy: to induce remission
• Consolidation: to mop up residual leukaemia cells
• Maintenance therapy (only in ALL): to keep patient in remission (for up to 2yrs)

Question 11

Bone marrow transplantation

Answer 11

• Autologous = own stem cell taken in remission
• Allogenic = matched sibling or unrelated donor
• Stem cells = from BM, peripheral blood or umbilical cord blood

Question 12

Outcomes in acute leukaemias

Answer 12

• Adults with AML: 80% remission, 50% cure
• > 60yrs with AML: outcomes not as good
• Children with ALL: 90% remission, 70-80% cure