Acute Myeloid Leukaemia

Question 1

What is the peak incidence?

Answer 1

65

Question 2

What percentage of acute leukaemias during adulthood are myelongenous?

Answer 2

80%

Question 3

It can occur as a primary disease or…

Answer 3

Following a secondary transformation of a myeloproliferative disorder

Question 4

What causes it?

Answer 4

None identified in most cases
Pre - existing haematopoietic disorder: myeloproliferative disorders, aplastic anaemia, myelodysplastic syndromes
Environmental - radiation, alkylating chemotherapy, smoking
Genetic - Down syndrome, Turner’s, Fanconi anaemia

Question 5

Describe the pathophysiology

Answer 5

Myeloid blasts more than 20% of bone marrow
Myeloid blasts proliferate and replace most of BM, crowding out normal haematopoiesis
Enter peripheral blood
Mestastasise throughout body - liver, spleen, LNs

Question 6

Describe the signs and symptoms

Answer 6

Marrow failure features: 
Anaemia
Frequent infections (while WCC may be high, functioning neutrophils may be low)
Thrombocytopenia- bleeding 
Bone pain

Infiltration: 
Hepatomegaly, splenomegaly 
Painless lymphadenopathy 
Gum hypertrophy 
Skin involvement - leukaemia Curtis 
CNS involvement

Question 7

How is AML classified?

Answer 7

M0
M1
M2 - myeloblastic with maturation t(8:21)
M3 - acute promyelocytic leukaemia t(15:17) 
M4
M5 - monocytic (gum infiltration) 
M6
M7

Question 8

What is the most common type of AML?

Answer 8

Myeloblastic with maturation
T(8:21)
Good prognosis

Question 9

Describe acute promyelocytic leukaemia

Answer 9

M3
Associated with DIC or thrombocytopenia 
Presents younger than other types (average age = 25) 
Auer rods
Good prognosis 
Can treat with vitamin A (ATRA)

Question 10

Does acute promyelocytic leukaemia have a good prognosis?

Answer 10

Yes

Question 11

What unfavourable prognostic factors are there?

Answer 11

Age > 60 
WBC > 100,000
Poor performance status 
Secondary AML 
More than 20% blasts after first chemo course 
Mutation of FLT3

Question 12

What does FBC show?

Answer 12

WCC often high but can be normal or low
Thrombocytopenia
Anaemia - normocytic, might be macrocytic is folic acid deficiency

Question 13

What is seen in peripheral blood smear?

Answer 13

Blast presence - although may be few so diagnosis depends on BM biopsy, immunophenotyping, cytogenetics
Some subtypes especially M3 exhibit Auer rods in blasts

Question 14

What investigations indicate increased cell lysis?

Answer 14

Electrolytes and metabolic markers 
Raised phosphate 
Hypocalcaemia 
Hyperkalaemia 
Increased LDH 
Increased uric acid

Question 15

What does bone marrow aspiration and biopsy show?

Answer 15

More than 20% blasts

Question 16

How is AML differentiated from ALL on biopsy?

Answer 16

Auer rod presence

Question 17

Immunophenotyping by flow cytometry show that majority subtypes positive for…

Answer 17

CD13, 33, 34, 117, HLA-DR

Question 18

How is it treated?

Answer 18

Induction: cytasine arabinoside and daunorubicin
Consolidation with same drugs

Allogenic cell transplant if not getting remission with chemotherapy

If M3 type give vitamin A and check for DIC

Question 19

If CNS involved, what can be done?

Answer 19

Intrathecal chemotherapy

Question 20

What is an allogenic stem cell transplant?

Answer 20

Stem cells collected from matching donor and transplanted into patient to suppress the disease and restore immune system.

The immune system and leukaemic cells first destroyed by cyclophosphamide and total body irradiation, then repopulate marrow with donor cells infused IV.

Cyclosporin +/- methotrexate used to reduce effect of new marrow attacking patient’s body (graft vs host disease)

Question 21

Is leukostasis more common in AML or ALL?

Answer 21

AML

Increased number of immature leukocytes, so viscosity of blood increased - increased risk of vessel obstruction and DIC

Question 22

Is AML myeloperoxidase positive ?

Answer 22

Yes unlike ALL