1) Leukaemia is a malignant blood disorder characterized by uncontrolled proliferation of abnormal white blood cells in the bone marrow, causing bone marrow failure and infiltration of organs. 2) The causes of leukaemia are largely unknown but may include genetic abnormalities, radiation exposure, chemicals, and viruses in some cases. 3) Leukaemia is classified based on the type of white blood cells involved (myeloid or lymphoid) and their level of maturation, with the most common forms being acute myeloid leukaemia and acute lymphoblastic leukaemia.

1. Leukaemia I & II
General & Etiology Causes
Uncontrolled proliferation of abnormal/ malignant
clone → Replacement of normal haemopoietic cells in
the bone marrow
Bone marrow disorder.
Malignant blood disorder.
Majority of leukaemia is unknown.
Accumulation of abnormal white cells in the BM, may
cause:
BM failure
Raised circulating white cell count
Infiltrate organs
Leukaemoid reaction:
Occurrence of peripheral blood picture resembling
that of leukaemia in a subject who does not have
leukaemia
1) Ionizing radiation:
AML,CML
Irradiation therapy for other malignancies →
myelodysplasia →acute leukaemia.
2) Chemicals:
Benzene, petroleum derivatives and alkylating agents
; bulsulphan, chlorambucil, chloramphenicol
3) Genetic abnormalities:
t(9,22)→CML
t(15,17)→ acute promyelocytic leukaemia
increase incidence of leukaemia : Down's Syndrome,
Fanconi's anaemia
4) Viruses:
HTLV I → T cell leukaemia/ lymphoma
HTLV II → Hairy cell leukaemia
AML classification with morphology
AML minimally differentiated ( FAB M0)-
No evidence of myeloid differentiation by morphology and light microscopy cytochemistry
Immunophenotypic studies, essential
AML without maturation (FAB M1)-
-The blasts constitute ≥ 90% of the non-erythroid cells
- > 3% of the blasts show SBB and MPO positivity
AML with maturation ( FAB M2) -
There is evidence of maturation in 10 % or more neutrophil precursors
Acute promeylocytic leukaemia (FAB M3)
-
Acute myelomonocytic leukaemia (FAB M4)
-shows proliferation of both neutrophil and monocyte precursors
Acute monoblastic and monocytic leukaemia ( FAB M5a and M5b)-
80% or more of the leukaemic cells are of monocytic lineage, including monocytes, promonocytes and
monoblasts
Acute Erythroid leukaemia (FAB M6)-
(-erythroid /myeloid or erythroleukemia M6a (pure erythroid leukaemia M6 b)
-These leukaemias are characterized by a predominant erythroid population

2. Acute Leukaemia Clinical features Diagnosis & laboratory investigation Management
AML. 1. Pallor, lethargy and dyspnoea
due to anaemia
2. Fever, malaise, features of
mouth, throat, skin, respiratory,
perianal or other infections,
including septicemia due to
neutropenia
3.Spontaneous bruises, purpura,
bleeding gums, menorrhagia and
bleeding from venepuncture sites
due to thrombocytopenia
4.A bleeding tendency due to
thrombocytopenia and
disseminated intravascular
coagulation (DIC) is characteristic
of AML M3
Due to organ infiltration
1.Moderate hepatomegaly,
splenomegaly
2.Gum hypertrophy and infiltration
(M4 & 5)
3.Skin infiltration, meningeal
syndrome (AML M4 & 5)
4.Lysosymes released by the blast
cells may cause renal damage in
AML M5
.In AML M6 (erythroleukaemia), many
erythroblasts may be found in the
blood film
.In AML M3, tests for DIC are positive
.Serum uric acid and LDH may be
raised
-A normochromic normocytic anaemia
-TLC may be decreased, normal or
increased
-Thrombocytopenia
-Blood film shows variable numbers of
blast cells, the blasts may contain
auer rods
Cytochemistry:
 Myeloperoxidase ( MPO)
activity is specific for myeloid
differentiation
 Sudan Black B (SBB ) reactivity
is similar to MPO in
myeloblasts and monoblasts
 Non-specific esterase ( NSE)
reactivity is diffuse in the
cytoplasm of monoblasts
Immunophenotype
 Immunophenotypic analysis
has a central role to
differentiate between AML-
M0 and ALL
 It may be performed
 By flow cytometry or
immunohistochemistry on the
slides
-Inform the patient /
family
-Start treatment ASAP
-Supportive care /
associated problems
-Remission Induction
cytotoxic chemotheray
-Remission
maintenance therapy

3. ALL Clinical features Laboratory investigation Management
-Common form of
leukemia in children
-incidence is highest
at, 3-4 years
-The common (CD10+
)
precursor B type, has
an equal sex incidence
ALL, L1: blast cells
are small, uniform,
high N:C ratio,
inconspicuous nucleoli
ALL, L2:
heterogeneous
population,
some blast cells larger
with lower N:C ratio
some are like those in
L1with high N:C ratio
ALL, L3: large cells
having vacuolated and
basophilic cytoplasm (
usually B-ALL ),
nucleoli prominent
Symptoms due to bone marrow
failure
1.Bone pain and arthralgia
2.Lymphadenopathy,
hepatomegaly and splenomegaly
are frequent
3.Meningeal syndrome:
- headache, nausea, vomiting ,
blurring of vision and diplopia
4.Testicular swelling
 Peripheral blood film and
CBC/FBC
 Bone marrow
examination, which in case
of acute leukaemias, is
hypercellular with marked
proliferation of blasts
 Lumbar puncture in
patients with meningeal
leukaemias
X-ray
- may reveal lytic bone lesions
mediastinal mass due to
enlargement of thymus/ and or
mediastinal lymph nodes
-Immunological markers and
chromosome analysis
 Supportive care:
 (Metabolic
complications,
hyperleucytosis,
infection control,
haematologic
support)
 Risk assessment
 Induction
chemotherapy, CNS
prophylaxis
 Consolidation
cemotherapy
 Maintenance
chemotherapy
.
Chronic lymphocytic
leukaemia
Proliferation and
accumulation of a
monoclonal
population of
abnormal lymphocyte
Express CD5 and CD23
Common in west
Elderly >50 y/o
Male> female
Majority: B-cell type
(95%)
Most patient asymptomatic
-Anaemia
-Lymphadenopathy (symmetrical
and painless)
-Immunological failure
-Splenomegaly & hepatomegaly
- autoimmune hemolytic anaemia
(10%)
-immune thrombocytopenia (ITP) -
5%
- haemorrhagic manisfestation
FBC: lymphocytosis
Smudge or smear cells
Normochromic normocytic
anaemia
BM biopsy: increase lymphocytes
Clonality study:
-immunotyping
-molecular analysis (IgG/TCR gene
rearrangement studies)
-chemotherapy
- monoclonal antibodies

4. Chronic Leukaemia Clinical features Laboratory
investigation
Management
Chronic Myeloid
Leukaemia
A clonal
myeloproliferative
disorder →rise from an
acquired genetic
change in pluripotent
stem cell
-overproduction of
neutrophils and its
precursor
Philadelphia
chromosome
-t(9,22)(q34,11)
95% CML; Ph' +ve
Fusion BCR-ABL genes
Has greater tyrosine
kinase
1) Chronic phase
- adult (40-60)
- anaemia
-splenomegaly
- hepatomegaly
- gout
(hyperuricaemia)
- hyperviscosity
syndrome (due to
leucocytosis)
- neutropenia,
thrombocytopenia
(not common)
2) Blast crisis
Transform → acute
leukaemia, mostly AML
Chronic phase
FBP: Leucocytosis
(increased WBC)
Usually >100 × 109
/l
Morphology: Myeloid
cells at all stages of
differentiation
Bone Marrow:
Hypercellular
Myelopoiesis is
increased (with few
blast is < 5%)
Neutrophil alkaline
phosphatase (NAP)
score : reduced
Cytogenetic analysis:
Ph-chromosome
Molecular analysis:
BCR-ABL fusion gene.
Chronic phase:
Hydorxyurea, Glivec/
Imatinib
Transplantation
- bone marrow /
peripheral blood stem
cell transplant.
Chronic lymphocytic
leukaemia
Proliferation and
accumulation of a
monoclonal population
of abnormal
lymphocyte
Express CD5 and CD23
Common in west
Elderly >50 y/o
Male> female
Majority: B-cell type
(95%)
Most patient
asymptomatic
-Anaemia
-Lymphadenopathy
(symmetrical and
painless)
-Immunological failure
-Splenomegaly &
hepatomegaly
- autoimmune
hemolytic anaemia
(10%)
-immune
thrombocytopenia
(ITP) -5%
- haemorrhagic
manisfestation
FBC: lymphocytosis
Smudge or smear cells
Normochromic
normocytic anaemia
BM biopsy: increase
lymphocytes
Clonality study:
-immunotyping
-molecular analysis
(IgG/TCR gene
rearrangement
studies)
-chemotherapy
- monoclonal
antibodies