Acute leukaemia

Question 1

What are the 2 main types of acute leukaemia ?

Answer 1

• Acute myeloid leukaemia (AML)
• Acute lymphoblastic leukaemia (ALL)

Question 2

What happens in acute leukaemias ?

Answer 2

• Starts from one abnormal cell (which resulting in monoclonal cell division - so the daughter cells also has a genetic marker (driver mutation or chromosomal change) that the parent cell has
• In acute leukaemias there is proliferation of these abnormal cells but the abormal cells cannot differentiate or mature resulting in a build up of immature precursor cells called ‘blasts’

Acute myeloid leukaemia (AML) is the clonal expansion of myeloid blasts in the bone marrow, peripheral blood, or extramedullary tissues. Bone marrow blasts of at least 20% are diagnostic. (AML can affect any of the myeloid precursor cells e.g. you could get a acute monoblastic leukaemia, acute megakaryoblast leukaemia etc)

Acute lymphoblastic leukaemia (ALL) is malignancy of lymphoid cells, affecting B or T lymphocyte cell lines, causing arrest of maturation and promoting uncontrolled proliferation of immature blast cells

Question 3

What level of blast cells in the bone marrow or peripheral blood signifies an acute leukaemia ?

Answer 3

>20%

Question 4

What does the build up of immature precursor cells in acute leukaemias eventually result in ?

Answer 4

They eventually spill out into the peripheral blood (where they can be looked at in the peripheral blood)

Question 5

What does the build up of blast cells in acute leukaemia result in ?

Answer 5

It gets in the way of normal cells differentiating resulting in a loss of normal cells:

• Loss of RBC’s ==> anaemia
• Loss of platelets ==> thrombocytopenia ==> bleeding
• Loss of neutrophils ==> recurrent infection

Question 6

What are the symptoms of AML ?

Answer 6

• Symptoms of marrow failure; anaemia, infection and bleeding
• Weakness
• Weight loss
• Bone and joint pain
• unusual and frequent bleeding, such as bleeding gums or nosebleeds
• easily bruised skin
• flat red or purple spots on the skin (petechiae)
• a feeling of fullness or discomfort in your tummy (abdomen), caused by hepatosplenomegaly

Question 7

What are the signs of AML seen on blood tests ?

Answer 7

• Anaemia
• WCC is often raised but can be normal or low
• Blast cells seen in the peripheral blood
• Thrombocytopenia
• Increaseed coagulation time
• Auer rods seen

Question 8

Who is typically affected by AML ?

Answer 8

More common in the elderly (>60 years)

Question 9

What are the 3 specific subgroups of AML that present with characteristic features that we should know about ?

Answer 9

• Monoblast AML - causes gum infiltration and bleeding
• Megakaryocyte AML - this is associated with downs syndrome and is the most common cause of AML in downs syndrome under 5yrs old
• An AML sub-type (acute promyelocytic leukaemia) has a specific chromosomal translocation t(15;17) and is associated with a coagulopathy (DIC

Question 10

What is the treatment of acute promyelocytic leukaemia ?

Answer 10

ALL trans retinoic acid

Question 11

What are the signs/symptoms of ALL ?

Answer 11

Pretty much the same as AML but more likely to have CNS involvement:

• headaches
• seizures (fits)
• vomiting
• blurred vision
• dizziness

May also present with lymphadenopathy

Question 12

What are the investigations which should be carried out in someone suspected of having acute leukaemia ?

Answer 12

1. Blood count and film - reduction in the normal components of blood, WCC may be high as the blast cells are registered as WCC on the machine, auer rods seen in AML. Despite the elevation of WCC many patients have severe neutropenia. Normocytic normochromic anaemia seen
2. Coagulation screen - increased coag time due to thrombocytopenia
3. Bone marrow aspirate - looking at the morphology of the cells, seeing if >20% of marrow is blast cells and also carry out immunophenotyping

Even if cells from AML and ALL look alike, they will express lineage-associated proteins: immunophenotyping is required for a definitive diagnosis

4. Cytogenetics (chromsome analysis) can the be done

Question 13

What are the surface markers present on B cell lymphoblasts which suggest it is a B-ALL i.e. B lymphoblast acute lymphoblastic leukaemia ?

Answer 13

C10,19 and 20

CD20+ ALL should have ratiuximab included in their treatment i.e. if its a B-ALL

Question 14

What are the surface markers on T lymphoblasts which indicate its a T-ALL?

Answer 14

Express markers ranging from CD2-8

Question 15

What is the treatment of ALL?

Answer 15

• Induction chemo - prednisolone (or dexamethasone), oncovin, anthracyclines, and/or crisantaspase
• If positive for philidelphia chromsome then use imatinub
• If CD20+ then also use ratuximab
• Dexrazoxane if recieving an anthracycline

Question 16

What is the treatment of AML?

Answer 16

Induction chemo - i.e., cytarabine plus an anthracycline) may be used, or mitoxantrone may be used in combination with cytarabine

Question 17

What age group does ALL usually occur in ?

Answer 17

• The ALL form of the disease most commonly occurs in younger children ages 2 to 8, but it can affect all age groups.
• Most kids with leukaemia have ALL

Question 18

What is the supportive treatment for patients give along side the main of the treatment in patients with acute leukaemia ?

Answer 18

• May need blood/platelet transfusion
• IV fluids
• Allopurinol to prevent tumour lysis syndrome
• Hickman line inserted for IV access

Question 19

What is the protein marker found on lymphoblasts indicating a lymphoid leukaemia ?

Answer 19

TdT

Question 20

Treatment of ALL and AML:

Multi-agent chemotherapy

ALL -can last up to 2-3 years:

• Different phases of treatment of varying intensity (induction, consolidation, intensification, maintenance)
• Targeted treatments in certain subsets

AML -Normally intensive:

• Between 2-4 cycles of chemotherapy (5-10 days of chemotherapy followed by 2-4 weeks of recovery) -Prolonged hospitalisation