1. Acute myeloid leukemia
Malignant clonal disorder of immature hematopoietic
cells characterized by abberant hematopoietic cellular
proliferation and maturation. Leukamic blasts may
express capabilities for maturation to a variable degree,
which lead to morphological heterogeneity

2. Acute leukemias Adults: acute lymphoblastic leukemia (ALL) 20%
acute myeloid leukemia (AML) 80%

3. Cytochemistry/ Immunology
Cytological criteria for the diagnosis
of acute myeloid leukaemia:
French-American-British (FAB) classification
FAB subtype
Microscopy
Cytochemistry/ Immunology M0
Blasts >30% of bone marrow nucleated cells
<3% of blasts positive for Sudan Black B or POX
Myeloperoxidase-positivity by ultrastructural cytochemistry
Myeloid immunological markers (e.g. CD13, CD33, myeloperoxidase) M1
Blasts >90% of bone marrow nonerythroid cells
> 3% of blasts positive for Sudan Black B or POX
Maturing granulocytic cells (i.e. promyelocytes to PMN cells)
< 10% non erythroid cells
(Pro)monocytes < 10% non-erythroid cells

4. Cytochemistry/ Immunology
Cytological criteria for the diagnosis
of acute myeloid leukaemia:
French-American-British (FAB) classification
FAB subtype
Microscopy
Cytochemistry/ Immunology
M2 with maturation
Blasts 30-89% of bone marrow nonerythroid cells
Maturing granulocytic cells (i.e. promyelocytes to PMN
cells) > 10% non erythroid cells
Monocytic cells (i.e. monoblasts to monocytes) < 20% of
nonerythroid cells and not meeting other criteria for M4 M3
Promyelocytes ( most hypergranular) >30% of bone
marrow nucleated cells
M3 variant
Promyelocytes (hypogranular or microgranular) >30%
of bone marrow nucleated cells

5. Cytochemistry/ Immunology M4 Acute myelomonocytic leukaemia
Cytological criteria for the diagnosis
of acute myeloid leukaemia:
French-American-British (FAB) classification
FAB subtype
Microscopy
Cytochemistry/ Immunology
M4 Acute myelomonocytic leukaemia
Blasts 30-89% of bone marrow nucleated cells
Granulocytic cells (i.e. myeloblasts to PMN
cells) > 20% non erythroid cells
Monocytic cells (i.e. monoblasts to monocytes) < 20% of
nonerythroid cells andperipheral blood monocytes > 5x109/l
(or)
Monocytic cells > 20% of nonerythroid cells and confirmed
by cytochemistry or elevated urinary lysozyme
Marrow resembling M2, but blood monocytes > 5x109/l and
confirmed by cytochemistry or elevated urinary lysozyme
Positive for SBB, POX, chloroesterase (granulocyte lineage)
+ -naphtyl esterase (monocyte lineage)

6. Cytological criteria for the diagnosis of acute myeloid leukaemia:
French-American-British (FAB) classification
FAB subtype
Microscopy
Cytochemistry/ Immunology
M5A
Acute monoblastic leukaemia
Blasts 30% of bone marrow nonerythroid cells
Bone marrow monoblastic component > 80% of nonerythroid cells
Monoblasts > 80% of bone marrow monocytic component
M5B
Acute monocytic leukaemia
Bone marrow monocytic component > 80% of nonerythroid cells
Monoblasts < 80% of bone marrow monocytic component

7. Cytological criteria for the diagnosis of acute myeloid leukaemia:
French-American-British (FAB) classification
FAB subtype
Microscopy
Cytochemistry/ Immunology M6
Acute erythro- leukaemia
Erythroblasts > 50% of bone marrow
nucleated cells
Blast >30% of bone marrow non
nonerythroid cells
Glycophorine A positivity M7
Acute megakayoblastic leukaemia
Blasts 30% of bone marrow nucleated
cells
Blasts demonstrated to be megakaryoblasts by immunological markers, ultrastructural morphology or cytochemistry

8. Acute myeloid leukemia Clinical features
Suddent onset of the disease and very fast progression
If not treated  death after a few months
Most of the common systemic manifestations, such a fatigue, weakness, fever and weight loss, are non-specific

9. Acute myeloid leukemia Clinical features
Infiltration of bone marrow by leukemic cells
supression of normal hematopoietic progenitor cells growth  granulocytopenia, thrombocytopenia and anemia
infection of skin, mucous membranes, gums, respiratory, GI and GU tracts
bleeding in skin, mucous membranes, gums, GI and GU tracts
fatigue, weakness

10. Acute myeloid leukemia Clinical features
The prevalence and degree of organ infiltration vary somewhat with the different types of leukemia
abdominal fullness (enlargement of the liver and spleen)
gum hypertrophy (AML-M4 and M5)
bone and join pain and tenderness
neurological symptoms: headache, nausea, vomiting, blurred vision, cranial nerve dysfunction (AML-M4 and M5)
DIC (AML-M3)

11. Acute myeloid leukemia Approximate frequency of organ infiltration
Percent on initial exam
Percent at autopsy
Lymph nodes
Liver
Spleen
Bone and joint
Lungs
Heart
CUN GI 10 40 35 2 5 1 - 50 90 27

12. Acute myeloid leukemia
The diagnosis of AML is primarily based on morphological (>30% of basts and suppression of other lineages) and cytochemical criteria
Immunophenotyping, cytogenetic analysis and molecular examination are employed to add specific information for a more precise diagnosis (e.g. to identify undifferentiated leukemias as being myeloid)

16. Acute myeloid leukemia Remission induction treatment
The mainstay drugs have been daunorubicin and cytosine arabinoside* given as a 3+7 day schedule
number of cycle 1-2
REMISSION 60-80%
*in the treatment of AML-M3 all-trans retinoic acid is also used
REMISSION 80%

17. Acute myeloid leukemia The aims of the induction treatment
obtain the complete remission (RC)*
and restoration of polyclonal hemopoiesis
* defined as reduction of the blast cells in the marrow < 5% (inapparent) and normalzation of the picture of the peripheral blood
 However, monoclonal hemopoiesis is still present!

18. Acute myeloid leukemia Principle of the treatment
CNS prophylaxis/treatment
if clinical symptoms suggest meningeal leukemia
AML-M4 or 5
patients < 18 years old
 combination of drugs administered intrathecally
(Ara-C plus Fenicort, MTX plus Fenicort) or
CNS radiotherapy

19. Acute myeloid leukemia Post-remission chemotherapy
The aims of the intensification treatment:
- elimination of residual disease
prolongation of the time of remission

20. Acute myeloid leukemia risk groups
Good risk disease
t(8;21), t(15;17) inv 16
Standard risk disease
Poor risk disease
- abnormalities of chromosome 5, complex changes, monosomy 7 and 3q-