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 Microscopy Cytochemistry/
subtype Immunology
• Blasts >30% of bone marrow nucleated cells Myeloid
M0 • <3% of blasts positive for Sudan Black B or POX immunological
• Myeloperoxidase-positivity by ultrastructural cytochemistry markers (e.g.
CD13, CD33,
myeloperoxidase)
• Blasts >90% of bone marrow nonerythroid cells
M1 • > 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
 Cytological criteria for the diagnosis
of acute myeloid leukaemia:
French-American-British (FAB) classification
FAB Microscopy Cytochemistry/
subtype Immunology
• 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
• Promyelocytes ( most hypergranular) >30% of bone
M3 marrow nucleated cells
• Promyelocytes (hypogranular or microgranular) >30%
M3 variant of bone marrow nucleated cells
 Cytological criteria for the diagnosis
of acute myeloid leukaemia:
French-American-British (FAB) classification
FAB Microscopy Cytochemistry
subtype / Immunology
• Blasts 30-89% of bone marrow nucleated cells Positive for
M4 Acute • Granulocytic cells (i.e. myeloblasts to PMN SBB, POX,
myelomono cells) > 20% non erythroid cells chloroesterase
cytic (granulocyte
• Monocytic cells (i.e. monoblasts to monocytes) < 20% of
leukaemia lineage)
nonerythroid cells andperipheral blood monocytes > 5x109/l + -naphtyl
(or) esterase
• Monocytic cells > 20% of nonerythroid cells and confirmed (monocyte
by cytochemistry or elevated urinary lysozyme lineage)
• Marrow resembling M2, but blood monocytes > 5x109/l and
confirmed by cytochemistry or elevated urinary lysozyme
 Cytological criteria for the diagnosis
of acute myeloid leukaemia:
French-American-British (FAB) classification
FAB Microscopy Cytochemistry
subtype / Immunology
• Blasts 30% of bone marrow nonerythroid cells
M5A • Bone marrow monocytic component > 80% of
Acute nonerythroid cells
monoblastic • Monoblasts > 80% of bone marrow monocytic component
leukaemia

M5B • Blasts 30% of bone marrow nonerythroid cells

Acute • Bone marrow monocytic component > 80% of
monoblastic nonerythroid cells
monocytic • Monoblasts < 80% of bone marrow monocytic component
leukaemia
 Cytological criteria for the diagnosis
of acute myeloid leukaemia:
French-American-British (FAB) classification
FAB subtype Microscopy Cytochemistry/ Immunology
• Erythroblasts > 50% of bone marrow
M6 nucleated cells Glycophorine A positivity
Acute erythro- • Blast >30% of bone marrow non
leukaemia nonerythroid cells

M7 • Blasts 30% of bone marrow nucleated Blasts demonstrated to be

Acute cells megakaryoblasts by
megakayoblastic immunological markers,
leukaemia 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 Percent on initial exam Percent at autopsy

Lymph nodes 10 50
Liver 40 90
Spleen 35 90
Bone and joint 2 5
Lungs 5 50
Heart 2 35
CUN 1 27
GI - 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 M0 M1 M2 M3 M4 M5 M6 M7

Peroxidase - + + + +/- - +/- -

(POX)
Sudan Black - + + + +/- - +/- -
B
Unspecific - - - - + + - -
esterases
PAS - - - - - - + -
 AML- immunocytology
FAB Immunological markers
M0 HLA-DR, CD33, MPO
M1 HLA-DR, CD13, CD33, MPO
M2 HLA-DR, CD13, CD33, CD15, CD34, MPO
M3 HLA-DR, CD33, CD15, MPO
M4 HLA-DR, CD13, CD14, CD15, CD33
M5 CD13, CD33, CD14, CD15, CD34
M6 CD13, CD33, glicophorin A
M7 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 BIAŁACZEK
(2)
Metoda: chemioterapia
2.

a/ AML - lek z grupy antracyklin i arabinozyd cytozyny („3+7”;

liczba kuracji 1-2)
REMISJA: 60-80%
UWAGA: w leczeniu AML-M3 stosuje się kwas
transretinowy (pochodna witaminy A)
REMISJA: ok. 80%
b/ ALL - sterydy, winkrystyna, lek z grupy antracyklin, L-
asparginazy (4-8 tygodni)
REMISJA: 70-85%
 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 BIAŁACZEK (7)
C. Leczenie wspomagające
 izolacja chorych

 selektywna dekontaminacja przewodu pokarmowego

 leczenie przeciwbakteryjne, przeciwgrzybicze,

przeciwwirusowe
 czynniki wzrostu

 leczenie substytucyjne preparatami krwi

 leczenie hiperurykemii (allopurinol, alkalizacja

moczu, nawodnienie)