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

Acute leukemias
Adults:
- acute limphoblastic leukemia (ALL) 20%
- acute myeloid leukemia (AML) 80%

Cytological criteria for the diagnosis

of acute myeloid leukaemia:
French-American-British (FAB) classification
FAB
subtype

Microscopy

M0

Blasts >30% of bone marrow nucleated cells

<3% of blasts positive for Sudan Black B or POX
Myeloperoxidase-positivity by ultrastructural cytochemistry

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

Cytochemistry/
Immunology
Myeloid
immunological
markers (e.g.
CD13, CD33,
myeloperoxidase)

Cytological criteria for the diagnosis

of acute myeloid leukaemia:
French-American-British (FAB) classification
FAB
subtype

Microscopy

Blasts 30-89% of bone marrow nonerythroid cells

M2 with Maturing granulocytic cells (i.e. promyelocytes to PMN
maturation
cells) > 10% non erythroid cells
Monocytic cells (i.e. monoblasts to monocytes) < 20% of
nonerythroid cells and not meeting other criteria for M4
M3
M3 variant

Promyelocytes ( most hypergranular) >30% of bone

marrow nucleated cells
Promyelocytes (hypogranular or microgranular) >30%
of bone marrow nucleated cells

Cytochemistry/
Immunology

Cytological criteria for the diagnosis

of acute myeloid leukaemia:
French-American-British (FAB) classification
FAB
subtype

Microscopy

Blasts 30-89% of bone marrow nucleated cells

M4 Acute Granulocytic cells (i.e. myeloblasts to PMN
myelomono cells) > 20% non erythroid cells
cytic
Monocytic cells (i.e. monoblasts to monocytes) < 20% of
leukaemia
nonerythroid cells andperipheral blood monocytes > 5x10 9/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

Cytochemistry
/ Immunology

Positive for
SBB, POX,
chloroesterase
(granulocyte
lineage)
+ -naphtyl
esterase
(monocyte
lineage)

Cytological criteria for the diagnosis

of acute myeloid leukaemia:
French-American-British (FAB) classification
FAB subtype

Microscopy

Blasts 30% of bone marrow nonerythroid cells

M5A
Bone marrow monocytic component > 80% of
nonerythroid cells
Acute
monoblastic Monoblasts > 80% of bone marrow monocytic component
leukaemia
M5B
Acute
monoblastic
monocytic
leukaemia

Blasts 30% of bone marrow nonerythroid cells

Bone marrow monocytic component > 80% of
nonerythroid cells
Monoblasts < 80% of bone marrow monocytic component

Cytochemistry
/ Immunology

Cytological criteria for the diagnosis

of acute myeloid leukaemia:
French-American-British (FAB) classification
FAB subtype
M6
Acute erythroleukaemia

M7
Acute
megakayoblastic
leukaemia

Microscopy
Erythroblasts > 50% of bone marrow
nucleated cells
Blast >30% of bone marrow non
nonerythroid cells

Blasts 30% of bone marrow nucleated

cells

Cytochemistry/ Immunology

Glycophorine A positivity

Blasts demonstrated to be
megakaryoblasts by
immunological markers,
ultrastructural morphology or
cytochemistry

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

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

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)

Acute myeloid leukemia

Approximate frequency of organ infiltration
Organ
Lymph nodes
Liver
Spleen
Bone and joint
Lungs
Heart
CUN
GI

Percent on initial exam Percent at autopsy

10
40
35
2
5
2
1
-

50
90
90
5
50
35
27
10

Acute myeloid leukemia

The diagnosis of AML is primarily based on
morphological (< 30% of basts and suppression
of other lineages) and cytochemical criteria
Immunophentyping, 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)

AML cytochemistry
Reaction
Peroxidase
(POX)
Sudan Black
B
Unspecific
esterases
PAS

M0 M1 M2 M3

M4

M5

M6

M7

+/-

+/-

+/-

+/-

AML- immunocytology
FAB
M0
M1
M2
M3
M4
M5
M6
M7

Immunological markers
HLA-DR, CD33, MPO
HLA-DR, CD13, CD33, MPO
HLA-DR, CD13, CD33, CD15, CD34, MPO
HLA-DR, CD33, CD15, MPO
HLA-DR, CD13, CD14, CD15, CD33
CD13, CD33, CD14, CD15, CD34
CD13, CD33, glicophorin A
CD41, CD61

AML- cytogenetics
The most frequent cytogenetic abnormalities :
trisomy 8, monosomy 7, monosomy/trisomy 2.;
-

inv 16 (AML-M4Eo); del (5q), del (7q); X or Y

translocations: t(15;17) - 70% AML-M3;
t(8;21) -AML-M2

ZASADY LECZENIA OSTRYCH BIAACZEK

(2)
Metoda: chemioterapia
a/ AML - lek z grupy antracyklin i arabinozyd cytozyny (3+7;
liczba kuracji 1-2)
REMISJA: 60-80%
UWAGA: w leczeniu AML-M3 stosuje si kwas
transretinowy (pochodna witaminy A)
REMISJA: ok. 80%
b/ ALL - sterydy, winkrystyna, lek z grupy antracyklin, Lasparginazy (4-8 tygodni)
REMISJA: 70-85%
2.

Acute myeloid leukemia

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

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!

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

Acute myeloid leukemia

Post-remission chemotherapy
The aims of the intensification treatment:
- elimination of residual disease
- prolongation of the time of remission

Acute myeloid leukemia

risk groups

Good risk disease

t(8;12), t(15;17) inv 16
Standard risk disease
Poor risk disease
- abnormalities of chromosome 5, complex changes,
monosomy 7 and 3q-

ZASADY LECZENIA OSTRYCH BIAACZEK (7)

C. Leczenie wspomagajce
izolacja chorych
selektywna dekontaminacja przewodu pokarmowego
leczenie przeciwbakteryjne, przeciwgrzybicze,
przeciwwirusowe
czynniki wzrostu
leczenie substytucyjne preparatami krwi
leczenie hiperurykemii (allopurinol, alkalizacja
moczu, nawodnienie)