Acute Leukemias
Characteristics
1.malignant transformationof a hematopoietic stem cell
2.rapid progressive
3.fetal without treatment
4.replacement of normal bone marrow by blast cells
5.Blast cells consist 90% of B.M and P. blood
6.Occurs in all ages
7.Clinical onset is sudden
8.Anemia and thrombocytopenia are mild to severe
9.WBC is variable (high, normal or low)
10.Organomegalyis mild
LABORATORY DIAGNOSIS of acute leukemiaspanel
1-Complete blood picture
-Anaemia
-White cell count
-Platelet count
2-Bone marrow examination -
Cellularity
-% of blasts
3-Cytochemical stains
e.gMyeloperoxidase, Sudan black B
4-Immunophenotyping
A panel of monoclonal antibodies
(CDs) are used to detect : myeloid
markers and lymphoid
markers (for B & T cells).
5-Genetic Analysis (karyotyping,
FISH and PCR)
Chromosomal analysis is important for the
diagnosis, classificationand follow up of
haematologicmalignancies.
Types of acute leukemia
1.Acute myelogenousleukemia (AML).
2.acute lymphoblastic leukemia (ALL)
3.Acute Myelomonocyticleukemia(AMML)
Site of leukemic cells accumulation
They can infiltrate any organ or site
1-Bone marrow---replace normal hematopoietic cells
2-Liver and spleen, lymph nodes
3-CNS, Kidneys and gonads
What occurs in these sites?
1-CNS function disorder
2-Bone marrow :
a)impaired normal cells production (RBC, WBC, PLTs)
b)Production of immature (blast) cells
Acute MyeloblasticLeukemia
AMLis a malignant, clonaldisease that involves proliferation of
blasts.
AML is:
1.It is a blood cancer
2.Failure to produce normal cells (Neutrophiletc)
3.Highly heterogeneous
4.Mostly in adult
5.Belong to myeloid group cancer mainly Neutrophils
6.There is no enough Neutrophilsfor bacteria killing
Bone
marrow
peripheral
Blood
Involved in
FAB classification
FAB CLASSIFICATION
Morphologic classification of AML is based on
1.Cellular differentiation ( What type of cell?) (granulocyte, monocyte,
erythroid, or megakaryocytic)
2.Extent of maturation (Myeloblast, promyelocyte, granulocyte)
1.M0 Minimally differentiated
2.M1 Myeloblastic
3.M2 Myeloblasticwith differentiation.
4.M3 Promyelocytic
5.M4 Myelomonocytic
6.M5 Monoblastic
7.M6 Erythroleukemia
8.M7 Megakaryocytic
Pathophysiology
Uncontrolled growth of blasts in marrow leads to
1.Stop normal cells production .
2.Appearance of blasts in peripheral blood.
3.Accumulation of blasts in other sites (CNS, Kidney , Liver, spleen).
4.Function disorders of many organs.
Metabolic effects of AML
1.Increase in uric acid ––>uric acid nephropathy
2.Release of phosphates ––> decrease in Ca
2+
and Mg
2+
Patient`s Symptoms (Clinical Features of AML)
1.Anemia(weakness, fatigue, dyspneaon exertion)
2.Bleeding(mucosal bleeding, purpura)
3.Infection(neutropenia––> infections
AML in brief
Cells defect: granular cells (Neutrrophils,Eosino.
Basophil, Monocyte)
Origin: Bone marrow
Ageof patient: adult
Acute leukemia cause morbidity and
mortality through :-
1.Deficiency in blood cell
number and function
2.Invasion of vital organs
3.Systemic disturbances by
metabolic imbalance
1-CBC Result
1-anemia(low Hb, PCV, RBC
2-Thrombocytopenia
3--WBC
Blood smear study
•RBC: Normocyticanemia
•PLTs:Lowcount -<10x10
9
/l
•WBC:
•myeloblast90%
•neutropenia
•Normal other cells 10%
•presence of Auer rods
presence of abnormal white
blood cells
<1.0x10
9
/l to >200x10
9
/l,
1.Normal count
2.Lower count
3.Higher count +
50% of patient has >100.000/cum
AML_Laboratory findings
Flowcytometryor immunophenotypinag AML
diagnosis
identify antigens present on the blast cells
Positive for
CD 13
CD 33
====
HLA-DR
CD34
Indication of AML
Indication of stem cells
2-Bone marrow aspirate-and biopsy
myeloblastis the predominant cell
Decrease in normal
1.erythropoiesis,
2.myelopoiesis,
3.megakaryocytes
3-cytochemistery staining
1-Sudan black stain (SBB): Positive
2-Myeloperoxidase stain: (MPO): Positive
3-Specific Esterase (ES): Positive
Positive: MPO
Positive: ES
Myeloperoxidase-(MPO)
Positive result-Brown black deposits
Chloracetate (Specific) Esterase -Myeloid Cell Line
Positive result:Reddeposit