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 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

Cytological criteria for the diagnosis of acute myeloid leukaemia:

French-American-British (FAB) classificationFAB

subtypeMicroscopy 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

Cytological criteria for the diagnosis of acute myeloid leukaemia:

French-American-British (FAB) classificationFAB

subtypeMicroscopy Cytochemistry

/ Immunology

M4 Acute myelomono

cytic 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)

Cytological criteria for the diagnosis of acute myeloid leukaemia:

French-American-British (FAB) classificationFAB

subtypeMicroscopy Cytochemistry

/ Immunology

M5A

Acute monoblastic leukaemia

• Blasts 30% of bone marrow nonerythroid cells

• Bone marrow monocytic component > 80% of nonerythroid cells

• Monoblasts > 80% of bone marrow monocytic component

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

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

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

• 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 Clinical features

Acute myeloid leukemiaApproximate frequency of organ infiltration

Organ Percent on initial exam Percent at autopsy

Lymph nodes

Liver

Spleen

Bone and joint

Lungs

Heart

CUN

GI

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

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)

2. Metoda: chemioterapiaa/ AML - lek z grupy antracyklin i arabinozyd cytozyny („3+7”;liczba kuracji 1-2)

REMISJA: 60-80%UWAGA: w leczeniu AML-M3 stosuje się kwastransretinowy (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 leukemiarisk 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)