Lecture 11: Malignant Blood disorders

Question 1

Major categories of Blood and marrow cancers?

Answer 1

Leukaemias - given their name due to the massively raised number of WBC present in the blood due to proliferation of bone marrow expanding and replacing normal marrow cells

Myeloproliferative neoplasms - Increased proliferation with maintained differentiation (eg. Polycythaemia is an increased RBC count that can be primary or often secondary to HF or COPD with hypoxia)

Lymphomas - cancer of the lymphoid tissue either metaststic spread or primary lymphoma (hodgkin or non-hodgkin lymphoma)

Myeloma (or multiple myeloma) - A cancer of the plasma cells (from B-cells) and patients present with bone marrow failure from infiltration with lytic bone lesions due to cytokines

Question 2

Categories of leukaemia?

Answer 2

Myeloid lineage = myeloid leukaemia

Lymphoid lineage = Lymphoblastic leukaemia

Can be ACUTE (AML and ALL) or CHRONIC

Question 3

Pathogenesis of Leukaemia? Eg of chromosomal abnormality?

Answer 3

• Congenital/inherited risk (eg. down syndrome)
• viral infections (not really apart from a very small number)
• Radiation
• Chemical/DNA damaging drugs

There isn’t one cause and in many cases it is unknown what the cause is BUT, cytogenic and molecular changes found in most leukaemias are able to be tested.

(eg. Philadelphia chromosome t9:22 is found in most cases of chronic myeloid leukaemia and some cases of acute leukaemia) - imatinib is now used for these patients and blocks the tryosine kinase receptors increasing life expectancy from 4/5 years to almost normal.

Question 4

occurrence of ALL and AML clinical presentation?

Answer 4

Occurs in all ages of people with the average age being in the 60s

ALL predominantly childhood (85%)

AML predominantly adulthood (85%)

2-3 cases per 100,000

Question 5

Signs and symptoms of acute leukaemia?

Answer 5

Presentation is due to bone marrow failre:

• Profound anaemia: fatigue, dyspnoea, chest pain
• Neutropenia: infection , slow wound healing
• Thrombocytopenia: bruising and bleeding (petechial bleeding)

Others are due to organ infiltration:

• Bone marrow: bone pain
• Englarged: liver, spleen, lymph nodes, gums

Question 6

How to make a diagnosis of Leukaemia?

Answer 6

CBC:

• low Hb - Anaemia
• WBC increased - due to circulating blasts (leukaemia cells) BUT low neutroophils
• severe thrombocytopenia

Bone Marrow Biopsy:

• Aspirate or Trephine (core biospsy)
• shows > 20% blasts cells/leukaemic cells (often we see >80%)

Specialised testing:

• immunophenotype
• chromosome testing
• molecular studies

Question 7

AL therapy? general/supportive care?

Answer 7

• Intensive transfusion support at a major hospital (red cells and platelets) - heavily dependent so often have to move into a bigger centre if they are in a rural region (**neutrophils can’t be transfused as they last such a short period of time)
• Managememtn of infection - ID and lab support, antibiotics
• Vascular access - tunneled venous catheters that can stay in and provide good access to the patients
• Patient and family support

Question 8

Chemotherapy for AL? Other useful treatment?

Answer 8

Induction therapy - to induce remission

Consolidation - to mop up residual leukaemia

Maintenance therapy (only ALL) - to keep in remission

Haematopoietic stem cell transplantation - on first presentation or on relapse.

• Autologous - own stem cells taken in remission
• Allogenic - matched sibling of unrelated donor (more common)
• Stem cells: bone marrow, peripheral blood or cord blood

Question 9

Improved outcomes for acute leukamia?

Answer 9

AML age >60

• Remission rate 75-80% with 45-50% long term remission

ALL in children

• Remission rate = 90% with 70-80% long term remission

The earlier the better (untreated 4-6 weeks) in acute cases and some benefit in certain cases of chronic.