Download Acute leukaemia

Acute leukaemia
Dr. MO Kehinde
Department of Medicine
CMUL/ LUTH
Acute Leukaemia
• These are a heterogeneous group of diseases
characterized by infiltration of the blood, bone
marrow and other tissues by neoplastic cells of
the haematopoietic system.
• There are two main types
• myeloid leukaemia and
• lymphoid leukaemia .
TABLE 1 The FAB classification
of acute leukemia
• Lymphoblastic (ALL)*
• L1 Small, monomorphic, high N: C ratio
(SCORES 0 , 1 or 2 ) +
• L2 Large, heterogenous, nucleolated, low
N: C ratio (Scores - 1, -2 or - 3)
• L3 Burkitt – cell type, basophilic,
vacuolated
Myeloid (AML)
• M0 Undiferentiated myeloblastic (requires cell markers )
• M1 Myeloblastic without maturation (requires
cytochemistry: peroxidase or SSB)
• M2
Myeloblastic with maturation
• M3
Hypergranular promyelocytic
• M3 – variant Micro – or hyper granular
bilobed promyelocytes
• M4 Myelomonocytic with both
granulocytic and monocytic differentiation
• M5 Monoblastic (M5a requires cytochemistry : ANAE
or ANBE ) and promonocytic- monocytic(M5b)
• M6
Erythroleukaemia ,with
> 50% erythroblasts
and < 30% blasts
• M7
Megakaryoblastic
(requires cell markers )
Diagnosis
• SBB=Sudan black B;
• ANAE= alpha naphthyl acetate esterase:
• ANBE=alpha naphthyl butyrate esterase
• A diagnosis of ALL now requires cell
markers to demonstrate B. or T lineage
commitment.
Conditions predisposing to
acute leukaemia
• Down’s syndrome { Transient
{ Persistent (ALL or AML)
• Genetic or constitutional
• Bloom’s syndrome
• Fanconi’s anaemia (AML)
• Ataxia telangiectasia (ALL, lymphoma
Conditions predisposing to
acute leukaemia
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Acquired
Myelodysplasia (AML)
Chemotherapy +radiotherapy ( MDS AML)
Chronic myeloproliferative disorders (CML,
PRV,myelofibrosis) (AML)
Aplastic anaemia (ALL)
Paroxysmal nocturmal haemoglobinuria (AML,
rarely ALL)
Abbreviation
• MDS= myelodysplastic syndrome;
• PRV= polycythaemia rubra vera;
CML=chronic myeloid leukaemia
Acute Leukaemias
• are defined pathologically as blast cell
leukaemias or malignancies of immature
haemopoietic cells.
• The bone cell marrow shows > 30% blast
cells and they are divided into two main
groups: Acute myeloid leukaemia (AML)
and acute Lymphoblastic Leukaemia
(ALL).
Acute Leukaemia
• There are two main age groups: Childhood (<
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15 years ) and adult (> 15 years).
A third group is that of adults aged > 60 years
because of their response to current treatment
protocols both for ALL and AML, is inferior and
because the Patients are not usually included for
the more radical approaches using autologous or
allogeneic bone marrow transplantation (BMT).
AML comprises about 80% of adult cases
Epidemiology
• (ALL and AML
• Incidence :
(1) Age differences (as above)
• (2) Urban industrialized and rural areas
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(commoner in industrialized than rural)
(3) Socio – cultural factors Common CD 10 +
form of ALL ( c ALL) less frequent compared
with T – All in African countries and in poorer
sections of the community in the USA (e.g Black
or Spanish)
Acute LeuKaemia
• (4) Environmental agents implicated in the
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induction of certain types of Leukaemia.
a. Ionising radiation
b. Chemical carcinogens especially
alkylating agents used for treatment of other
malignancies.
(5) Host susceptibility e.g. genetic disorders
(6) Blast transformation in pre existing
myeloproliferative disorders
(7) In Down’s syndrome.
Acute Leukaemia
• (8) Oncogenic viruses in causation of
human acute Leukaemia
• HTLV -1 ( human T – cell lymphoma virus
-1 ] directly implicated in adult – Tcell
leukaemia /Lymphoma.
Acute Leukaemia
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Ionizing radiation :
X-rays and other ionizing rays can induce
leukaemia (as observed in survivors
of the atomic bomb explosions in Hiroshima
and Nagasaki)
Chemicals
Two types of chemicals strongly suspected of
being leukaemogenic are
benzene and other petroleum derivatives
alkylating agents
Acute Leukaemia
• Chromosomes and oncogene
abnormalities:
• Cytogenetic abnormalities are found in
AML and ALL.
Clinical Features
• may include
• A General Symptoms of anaemia (Tiredness,
weakness lassitude, lethargy, shortness of breath).
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Bleeding
Infections
Anorexia, weight loss
Lymphadenopathy (very uncommon in AML except in
monocytic variant of AML )
Specific organ /system involvement
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Skin with nonspecific Lesions like
macules or papules, vesicles , pyoderma
gangrenosum,
• Neutrophilic dermatitis
• Leukaemic cutis
• Granulocytic sarcoma of the skin.
Acute leukaemia
• Differential diagnosis
• Septicaemia
• Miliary tuberculosis
• malignant histiocytosis
• Complications
• Worsening Continuous ill health
• Death
Relevant investigations
• Complete blood count, and ESR, reticulocyte
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count, comb’s test
Bone marrow examination
Biochemical tests such as serum electrolytes,
urea, creatinine, uric acid
Liver function tests.
Prothrombin time, partial thromboplastic time
Human Leucocyte antigen typing
HIV I and II.
Relevant investigations
• 1 Cytochemical tests such as
• (i) Peroxidase , Sudan black B
• (ii) Non – specific esterase reaction such
as alpha napthyl acetate esterace
• 2 Bone marrow cultures
• 3 Cytogenetic Findings
• 4 Electron microscopy
Relevant investigations
• Cell Markers e.g. using a panel of antibodies
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combined with flow cytometric analysis or the
alkaline phosphase – antialkaline phosphate
(APAAP) technique for the identification of
specification antigens and / or enzymes on the
membrane and / or in the cytoplasm or the
nucleus which identify the blast cells to be of
lymphoid or myeloid lineage
6 Abdominal scan or CT scan
Relevant investigations
• 7 Immunological Classification
• Terminal deoxy nucleotidyl transferase
demonstration in nucleus of B- and T –
lineage by means of a
• αN antibody using.
Management
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(a) Treatment objectives
. Induce remission to achieve complete remission
. Maintenance of disease free patients
(b) Non –drug treatment
Appropriate Nutrition.
- Adequate hydration (at least 3 liters/24 hours)
Provision of
(1) Erythrocytes transfusion as required
(2) Platelets concentrate transfusion as required
Maintenance of electrolyte balance.
Drug –treatment
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For Acute lymphoblastic leukaemia
Allopurinol 300mg daily p.o.
To use DVP or COAP
DVP i.e.
Daunorubicin 30mg/ m2 iv d8,15,22,29
Vincristine 1.4mg/ m2 to a maximum of 2mg iv
d8,15,22, 29
Prednisolone 60mg p.o.d 1-28
L-asparaginase 1000IU/ m2 i.v. 12,15,18,21,24,27,30,33.
Drug –treatment COAP
Cyclophosphamide 650mg/m2 1V day 1 and day8
day14 day 22
• Vincristine I.V 1.4mg/m2 to max . of 2mg.day
1 and day 8
day 14 and day 22
• Cytosine arabinoside S .C 50 mg/ m2 12 hourly
x 12 days or
• I/V bolus 100 mg/ m2 daily x 7 days
• Prednisolone 40mg/ m2 p.o. x 14/7
• Drugs are given every 28 days
Drug –treatment
• Number of courses= 3
• Criteria for complete remission assess patient
clinically and haematologically (including bone
marrow and blood examination)
• Nervous system prophylaxis
• Methotrexate intrathecal 12.5mg /m2 to a max
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15mg. x 5 doses over 3 weeks
i.e. twice weekly
Drug –treatment
• Consolidation; This is to be given on day
29
COAP
once provided WBC ≥ 1x109/ L
and Platelet count ≥ 100 x109/ L
• Maintenance; to have bone marrow
every 12 weeks
• 6 Mercaptopurine 75mg/ m2 daily p.o.
• Methotrexate 20mg/ m2 weekly p.o.
Drug –treatment
• Pulse therapy - (Intensification) To be
given every 3 months with
• Vincristine 1.4 mg/ m2 to a maximum of
2mg weekly day1 and day8
• Maintenance therapy to continue for 3
years if remission is maintained
• otherwise re assessment.
Acute Myeloblastic leukaemia
• a clonal disease that result from a acquired
genetic change in a pluri potential haemopoietic
stem cell . This altered stem cell proliferatial and
generates a population of differented cells that
gradually replaces normal haemopoiesis and
leads to a greatly expanded total myeloid mass.
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Use either TAD or COAP as shown below:
TAD
Cytarabine
100mg/ m2 (cont inf) d1+2 and
100mg/ m2
b.i.d. i.v. (30 min inf) d3-8
Thioguanine 100mg/ m2
b.i.d. p.o. every
12h 3-9
Daunorubicin 60mg/ m2
i.v.(1 h inf)
d3-5
AML
• Or COAP as shown below;
• Cyclophosphamide 650mg/m2 1V
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day 1 and
day8
Vincristine I.V 1.4mg/m2 to max . of 2mg.day
1 and day 8
Cytosine arabinoside S .C 50 mg/ m2 12 hourly
x 7 days
Prednisolone 40mg/ m2 p.o.
x 14/7
14 day cycle
AML
• Nervous system prophylaxis is not
required.
• Assess for remission after 3 courses.
• Maintenance
• Patient to have COAP every 6 weeks for 2
years.
• If there is CNS disease and it is monocytic
give intrathecal treatment as for ALL.
Thank you
• For
• Your
• Attention
ACUTE MYELOID LEUKAEMIA
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Def.Introduction
. Clonal malignant disease of the haemopoietic tissue
characterized by
. Proliferation of abnormal blast cells
. Impaired production of normal blood cell
:. Leukaemia blast cells
accumulate in the marrow. ↓
Suppress the proliferation & differentiation of normal
haemopoietic cells.
Classification of AML
( FAB classification)
• M0
Undifferentiated myeloblastic
• MI
Myeloblastci without maturation
• M2
Myeloblastic with maturations
• M2 BASO M2 with basophil blasts
• M3
Hypergranular pronyelocytic
• M3 Variant micro.or hypogranular
bilobed progranular
AML
• M4 .Myelomonocytic with both granulocytic and
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hypogranulocytic with both granulocytic and
monocytic differentation
M4 Eo M4 with bone marrow eosinoplilia
M5 Monocytic monoblastic (m5a) and
promonocytic –monocytic (M5b)
M6 Erythroleukaemia with > 50%
erythroblasts
M7
Megakaryoblastic
EPIDEMIOLOGY
• Age incidence:
• predominant form of leukaemia
• From middle age onward, the incidence
increases progressively
• Sex incidence
• It is slightly more common in male M > F
PATHOPHYSIOLOGY
• arises following malignant transformation
of a single haemopoietic progenitor
followed by cellular replication and
expansion of the transformed done.
• Defect in maturation beyond the
myeloblast or promyelocyte level in AML.
• Proliferating leukaemia cell accumulate in
BM ↓
PATHOPHYSIOLOGY
• Suppress normal haemopoiesis
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↓
• result in replacement of normal elements.
• ↓
• anaemia, infections & bleeding
complications.
• - Primarily proliferate in BM
PATHOPHYSIOLOGY
• circulate in the blood and infiltrate into
other
• tissues such as
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Lymph nodes, skin, gum,
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Liver viscera, CNS.
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Spleen
PATHOPHYSIOLOGY
• Growth. Advantages of Leukaemia cells
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Mechanisms
? unknown
• Postulates : - GF
production
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GF Receptors.
• . Factor Receptor coupling on normal versus
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Leukaemia cells may play a role
. Transforming genes or cellular oncogene
expressed in leukaemia cells code for GF
receptors
PATHOPHYSIOLOGY
• BM Failures due to
• Def. of normal stem cell differentiation
proliferation & maturation
• As a result of failure of production
humoral or microenviromental stimulators
• Mechanism of Neoplastic Transformation
• - Poorly understood .
• May involve a fundamental alteration of DNA
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conferring hereditable malignant xteristics to the
transformed cell,
In animal , Leukaemia can be induced by
retroviruses which either carry a transforming
gene (viral mcogene ) or integrate into specific
sites in DNA causing activation of cellular protooncogenes (insertional mutagenesis)