LEUKAEMIAS

Dr Shwe Sin
FMHS
Universiti Tunku Abdul Rahman
By the end of the lesson, the students should
be able to :
Define leukaemia.
State the classification of leukaemias based on
duration and cellular morphology.
Understand the F.A.B classifications and W.H.O
classifications of leukaemias.
Describe the leukaemogenesis of leukaemias.
Describe the pathogenesis, C/F, laboratory
findings of CML.
Describe the etiology, peripheral blood film
findings, laboratory tests of AML/ALL.
State the first line CD markers.
DEFINITION:
The leukaemias are group of disorders
characterized by the accumulation of
malignant white cells in the bone marrow
and blood.

Causes symptoms because of (1) bone

marrow failure and (2) infiltration of organs
 Etiology (Leukaemogenesis)
I. INHERITED FACTORS:
The incidence is greatly increased in some genetic diseases
particularly Downs syndrome, Fanconis anaemia etc
II. ENVIRONMENTAL INFLUENCES:
Chemicals e.g Benzene
Drugs e.g Chlorambucil
Radiation
Infections
Viruses e.g HTLV 1
Bacteria e.g Helicobacter pylori
Protozoa
III. THE GENETICS OF HAEMOPOIETIC MALIGNANCY:
Malignant transformation occurs as a result of genetic
mutations
CLASSIFICATION
According to:
I. Clinical course of disease:
(1) Acute leukaemia
(2) Chronic leukaemia
II. Type and degree of differentiation of
predominant leukaemic cell:
(1) Myeloid
(2) Lymphoid
FAB Classification (French-American-British)
I. Acute leukaemia:
(1)Acute Myeloid Leukaemia (AML)
(2)Acute Lymphoblastic Leukaemia (ALL)
II. Chronic leukaemia:
(1)Chronic Myeloid (Myelocytic/Granulocytic)
Leukaemia (CML)
(2)Chronic Lymphocytic Leukaemia (CLL)
 ACUTE LEUKAEMIAS
Usually aggressive
Characterized accumulation of blast cells
in the bone marrow (> 20%).
Dominant features is bone marrow failure
If untreated, rapidly fatal
But paradoxically, they may be easier to
cure than chronic leukaemias
I. Acute Myeloid Leukaemia (AML)
AML is the most common form of acute
leukaemia in adults and increasingly
common with age
It can occur in childhood as minor fraction
Most AMLs are associated with gene
mutations e.g t(15;17)
Myeloid blast cells make up >20% of bone
marrow
W.H.O classification of AML (2008)
AML with recurrent genetic abnormalities
AML with myelodysplasia-related changes
Therapy related myeloid neoplasm (t-AML)
AML, not otherwise specified
Myeloid sarcoma
Myeloid proliferations related to Downs
syndrome
FAB CLASSIFICATION OF ACUTE
LEUKAEMIA
ACUTE MYELOID LEUKAEMIA (AML) OR ACUTE NON-
LYMPHOBLASTIC LEUKAEMIA (ANLL)
M0 Undifferentiated myeloblastic
M1 Myeloblastic leukaemia without maturation
M2 Myeloblastic leukaemia with maturation
M3 Hypergranular promyelocytic Leukaemia
M4 Myelomonocytic Leukaemia
M4 Eo : M4 with bone marrow eosinophilia
M5 Monocytic Leukaemia
M5 a : Poorly differentiated type monoblasts with non granular
cytoplasm
M5 b : Well differentiated type Promonocytes and monocytes
in addition to monoblasts
M6 Erythroleukaemia
M7 Megakaryoblastic Leukaemia
Clinical Features:
Anaemia
Abnormal bleeding tendency
Infections
DIC especially AML M3
Gum hypertrophy, skin involvement and CNS
disease are characteristic of AML M4 and M5
Acute Myeloid Leukaemia (Myeloblasts)**- Large blast cells with
large nucleus and thin cytoplasm with granules. Reduced RBC
and platelets population.
Acute Myeloid Leukaemia- petechial
haemorrhages
 II. Acute Lymphoblastic Leukaemia
(ALL)
ALL is caused by accumulation of
lymphoblasts >20% in the bone
marrow.
It is most common malignancy of
childhood
Age : highest at 3-7 years with 75%
occurring before the age of 6
Revised French-American-British (FAB)
Classification:
L1 Homogeneous small lymphoblasts; scanty
cytoplasm, regular round nuclei, inconspicuous
nucleoli
L2 Heterogenous lymphoblasts; variable amount
of cytoplasm, irregular or cleft nuclei, large
nucleoli
L3 Large homogeneous lymphoblasts; basophilic
cytoplasm, round nuclei, prominent nucleoli,
cytoplasmic vacuolation
CLINICAL FEATURES
BONE MARROW FAILURE :COMMON
Anaemia (pallor, lethargy and dyspnoea)
Neutropenia (Fever, malaise and features of infection)
Thrombocytopenia (Spontaneous bruises, purpura, bleeding gums
and menorrhagia)
ORGAN INFILTRATION
Tender bones
Lymphadenopathy
Moderate splenomegaly
Hepatomegaly
Meningeal syndrome (headache, nausea, vomiting, blurred vision and
diplopia)
LESS COMMON
Testicular swelling
Mediastinal compression
 CHRONIC LEUKAEMIAS
They have slower progression than
acute leukaemias
Chronic leukaemias can be broadly
subdivided into myeloid and lymphoid
groups
I. CHRONIC MYELOID LEUKAEMIA
(CML)
SYNONYM : CHRONIC GRANULOCYTIC LEUKAEMIA,
CHRONIC MYELOCYTIC LEUKAEMIA, CHRONIC
MYELOGENOUS LEUKAEMIA
Divided into BCR-ABL 1 positive and BCR-ABL 1 negative
CML
CML with BCR-ABL 1 positive
It accounts for 15 % of leukaemias
Any age
Characteristic presence of philadelphia (Ph)
chromosome results from t(9:22) (q34:q11) translocation
CLINICAL FEATURES:
Most frequently between 40 and 60 years.
It may occur in children, neonates and old age
Male: female = 1.4 : 1
1. Weight loss, lassitude, anorexia and night sweat (due to
hypermetabolism)
2. Massive splenomegaly is nearly always present leading to
discomfort, pain and indigestion
3. Anaemia (pallor, dyspnoea, tachycardia)
4. Bruising, epistaxis, menorrhagia and haemorrhage from
other sites (abnormal platelet function)
5. Gout or renal impairment (hyperuricaemia)
6. Visual disturbances and priapism (rare)
PROGNOSIS
Average duration of survival : 3 4 years (1 10 years or
more)
80 % - die of blast transformation
Rest die of intercurrent infections & haemorrhage
II. CHRONIC LYMPHOCYTIC
LEUKAEMIA (CLL)
Peak incidence between 60 and 80 years of age
Occurs in older subjects
Male : Female = 2 : 1
Most cases are diagnosed when routine blood test is
performed
Symmetrical enlargement of cervical, axillary or inguinal
lymph nodes (most frequent) and usually discrete and
non-tender
Features of anaemia
Thrombocytopenia
Splenomegaly and hepatomegaly
Prone to infections (immunosuppression)
First line CD Immuno markers***
Myeloid markers: CD13, CD33, CD117
T cells markers: CD1, CD2, CD3,
CD4, CD8, Cd5, CD6, CD7
B cells markers: CD19, CD20, CD22,
CD9, CD10, CD79 and
 REFERENCES
Essential Haematology (A.V. Hoffbrand and P.A.H moss)
6th Edition
Robbins Basic Pathology, 9th Edition