Acute leukaemias

Dr Nilukshi Perera
Consultant Haematologist
 Leukaemia
is haematological malignancy in the leucocyte
lineage

.
DEFINITION :

Clonal malignant disorders characterized by the

proliferation of abnormal (leukemia)blast cells

and

impaired production of normal blood cells.

 Acute Leukemia
• Accumulation of blasts in the marrow
 Causes of Acute Leukemias
• Idiopathic (most)
• Underlying hematologic disorders
• Chemicals, drugs
• Ionizing radiation
• Viruses (HTLV I)
• Hereditary/genetic conditions
 Predisposing Factors
• Genetic Syndromes
– Down syndrome: 10-20 times increased incidence
(600 times in megakaryoblastic type)
– Bloom syndrome
– Neurofibromatosis
– Schwachman syndrome
– Ataxia Telangiectasia
– Klinefelter syndrome
 Classification of leukemia
Main classification

Chronic leukemia Acute leukemia

FAB

Lymphoid Myeloid Lymphoid Myeloid

L1 AML
M0
L2 M1
L3 M2
M3
M4
M5
M6
M7
 What Is Acute Leukemia?
• The acute leukaemias are a heterogeneous group of malignant disorders,
which are characterized by the uncontrolled clonal proliferation and
accumulation of poorly differentiated blast cells in the bone marrow and
other tissues.
• Thus replacement of normal bone marrow elements with abnormal
(neoplastic) blood cells.
• These leukaemic cells are frequently (but not always) present in the
peripheral blood stream.
• Subsequently there is a raised total blood count and evidence of bone
marrow failure (i.e. anaemia, neutoropenia, thrombocytopenia) are
ensues.
• In the acute leukaemias the blasts commonly invade reticuloendothelial
tissues including the spleen, liver and lymph nodes. They may also invade
other tissues, infiltrating any organ of the body.
• If left untreated, leukaemia eventually causes death.
 ALL
naïve

B-lymphocytes

Plasma
Lymphoid cells
progenitor T-lymphocytes

AML
Hematopoietic Myeloid Neutrophils
stem cell progenitor

Eosinophils

Basophils

Monocytes

Platelets

Red cells
 Pathophysiology of leukaemia
¯Protein
¯ vit
¯min
Weakness ,
Emaciation

Infiltration
Bone- pain BM Failure

tenderness S
L
LN
CNS
Anaemia infection Bleeding Skin

Coma –Hyperleukostasis
Mediastine
Hyperuricaemia - breakdown Bone
Joints
Neoplastic Proliferation of White Cells
Main types
• Acute Lymphocytic Leukemia (ALL)
• Acute Myelogenous Leukemia (AML)
• Chronic Lymphocytic Leukemia (CLL)
• Chronic Myelogenous Leukemia (CML)
 Acute leukaemias

Neoplastic proliferation of immature

cells ( blasts) in the marrow
(Blasts > 20 % in the bone marrow)
.
 Classification of leukaemia
AcuteChronic
• Aggressive clinical course • Chronic clinical course
• Need urgent treatment • May watch & wait
,treatment depending on
• Dominant cell is an stage of disease
immature blast cell

• Classified to lymphoblastic
and myeloblastic • Dominant cell is more
mature

• Classified to lymphatic and

myeloid
• Clinical features are often due to:
1.Bone marrow infiltration due to blast cell
proliferation causing
Anaemia: Pallor, tiredness
Thrombocytopenia: gum bleeding, purpura
Neutropenia: Infections, fever, pharyngitis
2.Organomegaly: ALL-lymphadenopathy
AML-hepato/splenomegaly
Gum hypertrophy-M4
3.Bone pain/joint pain
ACUTE LEUKAEMIA - PURPURA
Gum hypertrophy
ACUTE MYELOID LEUKAEMIA – GUM HYPERTROPHY
Lymphadenopathy,
 WHAT IS A BLAST?
Blast Normal cell

Cell larger than normal Small in size

More nucleoli No nucleoli

Nuclei less condensed ( open chromatin Condensed nucleus ( tight chromatin

pattern) pattern)
 Two type of blasts
Myeloblast Lymphoblast
Larger cell than lymphoblast Smaller cell compared to myeloblast

2-3 or more nucleoli No nucleoli or only one nucleolus

Very loose chromotin pattern (very open Chromatin more condensed than
nucleus) myeloblast

Granules + , Auer rods + No granules No Auer rods

Sudan black stain positive for the PAS stain positive

granules
Auer rods in myeloblasts
An Auer rod
Myeloblasts are Sudan Black positive
Sudan stain
positive myeloblasts
 Laboratory investigations
• Full blood count:
WBC: increased
DC: neutropenia
blast cells
Platelet count: low
Red cell count: low
Hb:low
• Blood picture
 Bone marrow biopsy
• Hypercellular
fragments
• Erythropoiesis: 
• Granulopoiesis: 
• Megakaryocytes: 
• Blast cells more than
20%
• Flowcytometry/immuno
phenotyping
• Cytogenetics
 Acute lymphoblastic leukaemia
• Common in children
• 85% in children
• 15% in adults
• Peak age is 3 - 4 yrs
• Peak reduces by 10 yrs
• Older age grp 40 yrs.
• Treatable and potentially curable
ALL
 ALL Clinical features
• Recurrent infections
• Anaemia
• Petechiae, purpura due to low platelets
• Bone pain
• Gen. lymphadenopathy
• Hepato-splenomegaly
• Headache, visual disturbances, cranial nerve
involvement(meningeal syndrome)
 .
Less common presentations
• Testicular deposits (painless)
• Joint deposits
• Features of hyperuricaemia
• Mediastinal widening and compression( in
Thymic (T) ALLs
 Differential diagnosis: clinically
• Other causes of ulceration of mouth
• Infectious mononucleosis:
sore throat
lymphadenopathy
splenomegaly

• Joint and bone pain:

Acute osteomyelitis
Rheumatic fever
 Types of ALL
• ALL L 1
• ALL L 2
• ALL 3
 Prognosis
Good Bad
WBC count at presentation Low High > 20 x 10 9 /i
Sex Female Males
Age 2 - 10 yrs < 2 yrs
> 10yrs
CNS CNS disease bad
Remission On D 7 , D 14
 Acute Myeloid leukaemias
• Commonest acute leukaemia in adults
80 % 15 yrs
20 % children and infants
• Poor response
• Full response is less common compared to ALL
 Myeloid maturation

myeloblast promyelocyte myelocyte metamyelocyte band neutrophil

MATURATION
Adapted and modified from U Va website
 Acute Myeloid Leukaemia
• FAB classification
M1-no differentiation
M2-minimal
differentiation
M3-promyelocytic
M4-myelomonocytic
M5-monocytic
M6-erythroid
M7-megakaryocytic
AML myeloblastic (M1)
AML
Auer rods in AML
 Clinical features
• Same as ALL except
• Myeloblastic chloromas ( solid tumor around
eyes, spinal cord,) specially in M2
 Investigations in acute leukaemia
• FBC
• Blood picture
• Bone marrow examination/flow cytometry &
genetic studies
• CSF for malignant cells
• X Rays CXR mediastinal widening,
Lytic bone lesions
 Bone marrow is sent for
• Morphology
• Special stains - cytochemistry -Sudan Black ,PAS
• Immunophenotyping ( test is done on Flow
cytometry machine) B lymphoblasts CD 10,20
T lymphoblasts DC 3, 7 etc
AML cells CD 13,33,
.Cytogenetic studies and molecular genetic studies
sometimes necessary for prognosis and diagnosis of
types
 Treatment of Acute leukaemias
• Supportive therapy

• Specific therapy
 Supportive therapy
• Psychological support
• Early treatment of infections
• Central venous line - and its management
• Red cell and platelet support
• Treatment of hyperuricaemia
• Anti emetics
 .
• Chemotherapy – aim is to kill all leukaemic cells
in the marrow and hope that a new stem cell
will emerge to produce normal cells

• Bone marrow transplant – aim is to wipe out all

leukaemic cells from the body by chemo and
radiotherapy and introduce a new stem cell
(Donor stem cell) which will home in the bone
marrow and produce normal haemopoesis
 Specific therapy for ALL
• If effectively treated 80 -90% achieve remission
• Chemotherapy given in 3 phases
• Induction of remission
• Intensification - ( to destroy residual leukaemic
cells)
• Maintenance – 2-3 yrs ( to prevent leukaemic cells
appear over a long period)
• CNS prophylaxis
• BMT done in 2nd remission and in bad phenotypes
 Specific therapy for AML
• Poor remission rates
• Induction
• BMT in 1st remission
• No CNS prophylaxis
• No maintenance therapy
Jemshidi trephine & Salah aspiration needle
Disposable BM needles
Questions ?
THANK YOU