DIAGNOSIS OF LEUKEMIA

Tri Ratnaningsih

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 Outline

• Introduction
• Sign And Symptom
• Diagnosis
• Prognosis And Therapy Monitoring

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 Phlebotomy – composition of blood

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 Blood smear

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normal blood cells

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 CLASSIFICATION OF WBC DISORDERS

WBC disorder

Quantitative Qualitative

Proliferave Leukopenia
disorder

Reactive Neoplastic

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 QUANTITATIVE DISORDERS OF LEUKOCYTES

Leukocytosis:
increase in the
total number of
leukocytes in the
blood more than
11,000/cu mm (11
× 109/L).

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 QUANTITATIVE DISORDERS OF LEUKOCYTES

Leukopenia: total
leukocyte count is
less than 4,000/cu
mm (4 × 109/L)

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 Pathogenesis
mutation of the Abnormal leukemic cells
bone marrow & impaired production of
pluripotent or most neoplastic expansion normal RBC, neutrophils,
primitive stem cells and platelets

The mutant clone may leukemic cells spill into

demonstrate unique the peripheral blood
morphologic, cytogenetic, and invade the
and immunophenotypic reticuloendothelial tissue

features that can be used to

aid in the classification of the
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particular type of leukemia
 Risk factors for acute leukemia

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 Outline

• Introduction
• Sign And Symptom
• Diagnosis
• Prognosis And Therapy Monitoring

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 Sign And Symptom

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 Comparing Acute And Chronic Leukemia

The initial evaluation of leukemia is initially made

by:
1. Noting the onset of symptoms
2. Analyzing the complete blood count (CBC) results
3. Observing the type of cell that predominates (cell
lineage)
4. Assessing the maturity of cells that predominate

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 The onset of symptoms

Acute leukemia Chronic leukemia

a quick onset a slow, insidious course
may occur at any age Usually seen in adults

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 Analyzing the complete blood count (CBC) results

Neoplastic cells take over  CBC results

will commonly show a decreased (anemia
and thrombocytopenia

The level of anemia and thrombocytopenia

tends to be more severe in acute leukemia.

Leukocytosis is a hallmark feature of chronic

leukemia, and because the spleen also becomes a site
of extramedullary (outside of the bone marrow)
hematopoiesis, prominent hepatosplenomegaly is
most often associated with chronic leukemia
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 Assessing the
H maturity of cells that
predominate
E
M
A
T
O Acute leukemia
blasts or other immature
P cells predominate
O
Chronic leukemia
I predominance
E of more mature cell
types
S
I
S
 Observing the type of cell that predominates (cell lineage)

myeloid stem cell  granulocytes, monocytes, megakaryocytes, and

erythrocytes : myeloid leukemias can involve proliferation of any
stage of these four cell lines
lymphoid stem cell  gives rise solely to lymphocytic lineage cells
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 Major categories of leukemia

Acute myeloid leukemias

Acute lymphoblastic
The cell lineage and leukemias
the maturity of cells
that predominate
Chronic myelocytic
leukemias

Chronic lymphocytic
leukemias

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 Outline

• Introduction
• Sign And Symptom
• Diagnosis
• Prognosis And Therapy Monitoring

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 Diagnosis of Acute Leukemia

Presently the diagnosis of acute leukemia requires the

presence of 20% or more blasts in the bone marrow
(WHO criteria)

The subclassification of acute leukemia is based on:

1. Morphology
2. Cytochemistry
3. Immunophenotyping
4. Cytogenetics (Karyotyping) and
5. Molecular Genetics

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 Morphology

Blast cells have following

morphological features:
1. Larger/bigger than normal
counterpart
2. High N:C ratio.
3. Nucleus is large, immature Morphology of blast cells
having open chromatin and
1 to 5 nucleoli.
4. Thin rim to moderate
amount of cytoplasm which
often appear atypical

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 Cytochemistry

is the study of chemical elements found in the cytoplasm of the cells

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 Cytochemistry

Cytoplasm of ALL L2 with block feature for Granulocytic differentiation is revealed by

PAS cytoplasmic positivity for Sudan black B

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 Differences between myeloblast and lymphoblast based on
morphology and cytochemistry

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 Revised FAB classification of acute myelogenous
leukemias (AML)

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 FAB classification of acute lymphoid leukemias (ALL)

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 Immunophenotyping

The leukemic cells express cell

surface and cytoplasmic antigens
which can be detected by using
monoclonal antibodies (MCAs)
directed against those antigens

Uses:
 To distinguish ALL from AML
 To distinguish B or T lineage in
ALL

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 Cluster of Differentitation

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 Cluster of Differentitation

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 Cluster of Differentitation

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 Internal components of
flowcytometer (fluida,
optic, electronic system)
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 How flow cytometry data are graphed.
 LL, cells negative for both x- and y-axes.
 UR, cells positive for both x- and y-axes.
 UL, cells positive for y-axis and negative for x-axis.
 LR, cells positive for x-axis and negative for y-axis.
Different CD antibodies are placed on the x- and y-axes
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 Useful panel of monoclonal antibodies
(MCAs) for differentiating AML from ALL

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 Cytogenetics

study of chromosomes, their structure and their inheritance.

One of the ways of studying cytogenetics is by karyotyping.

Cytogenetic analysis is important for determination of

prognosis and selection of postremission therapy.

WHO has incorporated cytogenetic abnormalities in its

classification of acute leukemias.

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Karyotype; human chromosome number
submetasentrik metasentrik dan submetasentrik berukuran sedang, dan X
berukuran besar

metasentrik
berukuran besar

akrosentrik berukuran
sangat kecil dan metasentrik metasentrik dan metasentrik
akrosentrik berukuran memiliki satelit kecuali berukuran submetasentrik ukuran sedang
sedang dan memiliki satelit. kromosom Y sangat kecil berukuran kecil
 Chromosomal abnormalities

• Kelainan kromosom yg cukup besar untuk dapat

dilihat dengan mikroskop cahaya  4 Mbp
• Klasifikasi:
1. numerik a.l. polyploidi (triploidi, tetraploidi)
trisomi 13, 18, 21
monosomi X
2. struktural a.l. delesi, translokasi, inversi,
ring

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 AML with t(8; 21)(q22;q22); (AML/ETO)

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 Outline

• Introduction
• Sign And Symptom
• Diagnosis
• Prognosis And Therapy Monitoring

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 Prognosis And Therapy Monitoring

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 Tumor lysis syndrome (TLS)

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 Summary:
• Leukemia is a stem cell neoplasm
characterized by diffuse replacement of
bone marrow with blast cells and
immature white blood cells in
circulation.
• WHO classification which requires
presence of 20% or more blasts for the
diagnosis of acute leukemia.
• The subclassification of leukemia is
based on cellular morphology,
cytochemistry, immunophenotyping,
molecular genetics and cytogenetics.
• The clinical features are mainly due to
bone marrow failure, leukostasis and
coagulopathies

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  Bernadette F. Rodak dan
Jacqueline H. Carr. Clinical
Hematology Atlas, 4ed,
2013, Saunders Company
 Ramadas Nayak dan
Sharada Rai. Essentials In
Hematology And Clinical
References: Pathology, 2ed, Jaypee
Brothers Medical
Publishers (P) Ltd, New
Delhi, India
 Betty Ciesla. Hematology in
practice. 2007, Davis
Company, Philadelphia,
USA

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