Module Blood and Lymph

2011/2012
UKMMC
LEUKAEMIA I & II

LEUKAEMIAS

A heterogeneous group of malignant

blood disorders - Malignant
haemopoietic progenitor/stem cell.

Uncontrolled clonal proliferation of

malignant cells of haematopoietic
origin.

Leukaemias

Proliferation of abnormal / malignant

clone

Replacement of normal haemopoietic

cells in the bone marrow
Bone marrow failure
Infiltrate other organs and proliferates
(organomegaly, CNS, skin infiltration)

Leukaemias - Etiology

Majority of leukaemias - unknown.

Increase incidence of leukaemia

in relation to certain factors.

Evolution of leukaemia - is a
multistep process.

Leukaemias
* Ionizing radiation (quantity: large doses)
* Chemicals
* Genetic abnormalities
(& oncogenes)
* Viruses : eg: HTLV I T cell leukaemia/lymphoma
(first described in
Japan)
HTLV II Hairy cell leukaemia
* Others - ?

Ionizing Radiation
First identifiable agent associated with
induction of leukaemias:
AML, CML
Irradiation therapy for other
malignancies myelodysplasia
acute leukaemia (eg: AML)
Chemicals
Benzene, petroleum derivatives and
alkylating agents; bulsulphan,
chlorambucil, chloramphenicol etc etc

Genetic abnormalities
Examples:
Translocation t(9:22) in chronic
myeloid leukaemia
t ( 15,17) in acute promyelocytic
leukaemia
Some genetic disorders associated
with increased incidence of leukaemia:
Downs Syndrome, Fanconis anaemia

Leukaemia - Classification
LEUKAEMIA:

Acute Chronic
Lymphoid
Myeloid
On the basis of the degree of cell
differentiation, onset and clinical course.

Acute Leukaemias:

eg:
Acute Lymphocytic Leukaemia (ALL)
Acute Myeloblastic Leukaemia (AML)
Chronic leukaemias:

eg:
Chronic Myeloid Leukaemias (CML)
Chronic Lymphocytic leukaemias
(CLL)
Others

ACUTE LEUKAEMIAS

Malignant disorder
Increase - immature haemopoietic
cells
Blasts
Arise de novo
A terminal event of pre-existing
blood disorders - PRV, MDS.

Acute Leukaemias: Classification

1) French-American-British (FAB) Classification 1976
(based on morphology and
cytochemistry)
ALL - L1, L2, L3
AML- M0 - M7
Old Classification
2) WHO classification
2) WHO Classification
- recent/new
- more comprehensive
- molecular, cytogenetic markers

Clinical Features

Effects due to:

1) Bone marrow infiltration by leukaemic blasts

anaemia, leucopenia, thrombocytopenia.
(and its complications).
2) Tissue (organ) infiltration

Clinical features
Effects and complications:
Anaemia
Thrombocytopenia
Neutropenia/leukopenia
Organ involvement/ failure

Particular subtypes of acute leukaemias:

EXAMPLES:

AML-M3 (acute promyelocytic leukaemia)

Increase incidence of disseminated
intravascular coagulation (DIC) & hemorrhage.
ALL CNS involvement > common in ALL than
in AML
Testicular involvement > common in ALL.
AML-M5
soft tissue infiltration: gums, skin,
CNS.
T- ALL Mediastinal mass

Diagnosis
Clinical
Laboratory

Laboratory Investigations
* Full blood picture:
- anaemia
- neutropenia, lymphopenia
- thrombocytopenia
(with or without presence of blasts)

Investigation (cont)

BM aspiration/trephine biopsy :
Reduced normal haemopoietic cells
Predominant cells in marrow = blast
cells

Cytochemical analysis :
differentiates AML and ALL
Myeloperoxidase, Sudan black.
Peroxidase Positive:
AML

Peroxidase negative:
ALL blasts

Immunophenotyping: use
monoclonal antibodies.
* Cytogenetic analysis
* Electron Microscopy
* Molecular analysis

Management

General / supportive treatment.

Chemotherapy.
Radiation, CNS prophylaxis(ALL)
Stem cell transplantation

AML-M3 (acute promyelocytic

leukaemia)
All-trans retinoic acid (ALTRA) to
induce differentiation
Chemotherapy / Transplantation

CHRONIC MYELOID LEUKAEMIA (CML)

A clonal myeloproliferative disorder,

rise from an acquired genetic
change in
pluripotential stem
cell.

Gross overproduction of neutrophils

and its precursors.

CML

Hallmark of CML : Philadelphia

chromosome
- the (9,22)(q34,q11) translocation.
95% CML:(Ph) positive.

The (9,22)(q34,q11) translocation:

Fusion BCR-ABL genes
has greater tyrosine kinase
activity: oncogenic growth factor

CML
Clinical Phase:
1) Chronic
2) Blast crisis
(transform acute leukaemia, mostly AML)

CML : chronic phase

Adults (40-60)

anaemia
splenomegaly (massive)
hepatomegaly
gout (hyperuricaemia)
hyperviscosity syndrome (due to leucocytosis)
neutropenia, thrombocytopenia (not common)
others..

CML (chronic phase) Investigations

FBP :
Leucocytosis (WBC)
usually > 100 x 10 9/l
Morphology : myeloid cells at all stages
of
differentiation

Lab. Investigations:

Bone marrow :
Hypercellular
Myelopoiesis is increased.
(increase myeloid series)
(with few blasts which is less than
5%
blasts)

Investigations :

Neutrophil alkaline phosphatase (NAP) score : reduced

Cytogenetic analysis : Ph-chromosome

Molecular analysis (bcr-abl fusion gene)

CML - TREATMENT
Chronic phase:
hydroxyurea, Glivec/Imatinib
- Transplantation
(Bone Marrow / Peripheral blood
stem cell transplant)

Chronic Lymphocytic Leukaemia

(CLL)

Proliferation and accumulation of a monoclonal

population of abnormal lymphocytes.

Common : West
Majority elderly >50 years
Male preponderance
Majority : B-cell type (95%)

CLL - Clinical Features

Common:
anaemia
lymphadenopathy
infections - persistent / severe
splenomegaly
autoimmune haemolytic anaemia 10%
immune thrombocytopenia (ITP) - 5%
haemorrhagic manifestations

Diagnosis : Clinical & Laboratory

Investigations:
Full blood picture:
lymphocytosis.
Bone marrow biopsy: lymphocytes
Clonality study :
- immunological study
(immunotyping)
- molecular analysis
(eg: IgG /TCR gene rearrangement studies).