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Acute leukaemia

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Acute leukaemia Dr. MO Kehinde Department of Medicine CMUL/ LUTH Thank you For Your Attention ACUTE MYELOID LEUKAEMIA Def.Introduction . Clonal malignant disease of ... – PowerPoint PPT presentation

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Title: Acute leukaemia


1
Acute leukaemia
  • Dr. MO Kehinde
  • Department of Medicine
  • CMUL/ LUTH

2
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 .

3
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

4
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

5
  • M4 Myelomonocytic with both granulocytic and
    monocytic differentiation
  • M5 Monoblastic (M5a requires cytochemistry
    ANAE or ANBE ) and promonocytic- monocytic(M5b)
  • M6 Erythroleukaemia ,with gt 50
    erythroblasts and lt 30 blasts
  • M7 Megakaryoblastic (requires cell markers )

6
Diagnosis
  • SBBSudan black B
  • ANAE alpha naphthyl acetate esterase
  • ANBEalpha naphthyl butyrate esterase
  • A diagnosis of ALL now requires cell markers to
    demonstrate B. or T lineage commitment.

7
Conditions predisposing to acute leukaemia
  • Downs syndrome Transient

  • Persistent (ALL
    or AML)
  • Genetic or constitutional
  • Blooms syndrome
  • Fanconis anaemia (AML)
  • Ataxia telangiectasia (ALL, lymphoma

8
Conditions predisposing to acute leukaemia
  • Acquired
  • Myelodysplasia (AML)
  • Chemotherapy radiotherapy ( MDS ? AML)
  • Chronic myeloproliferative disorders (CML,
    PRV,myelofibrosis) (AML)
  • Aplastic anaemia (ALL)
  • Paroxysmal nocturmal haemoglobinuria (AML, rarely
    ALL)

9
Abbreviation
  • MDS myelodysplastic syndrome
  • PRV polycythaemia rubra vera CMLchronic
    myeloid leukaemia

10
Acute Leukaemias
  • are defined pathologically as blast cell
    leukaemias or malignancies of immature
    haemopoietic cells.
  • The bone cell marrow shows gt 30 blast cells and
    they are divided into two main groups Acute
    myeloid leukaemia (AML) and acute Lymphoblastic
    Leukaemia (ALL).

11
Acute Leukaemia
  • There are two main age groups Childhood (lt 15
    years ) and adult (gt 15 years).
  • A third group is that of adults aged gt 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

12
Epidemiology
  • (ALL and AML
  • Incidence (1) Age differences (as above)
  • (2) Urban industrialized and rural areas
    (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)

13
Acute LeuKaemia
  • (4) Environmental agents implicated in the
    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 Downs syndrome.

14
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.

15
Acute Leukaemia
  • 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

16
Acute Leukaemia
  • Chromosomes and oncogene abnormalities
  • Cytogenetic abnormalities are found in AML and
    ALL.

17
Clinical Features
  • may include
  • A General Symptoms of anaemia (Tiredness,
    weakness lassitude, lethargy, shortness of
    breath).
  • Bleeding
  • Infections
  • Anorexia, weight loss
  • Lymphadenopathy (very uncommon in AML
    except in monocytic variant of AML )

18
Specific organ /system involvement
  • Skin with nonspecific Lesions like macules or
    papules, vesicles , pyoderma gangrenosum,
  • Neutrophilic dermatitis
  • Leukaemic cutis
  • Granulocytic sarcoma of the skin.

19
Acute leukaemia
  • Differential diagnosis
  • Septicaemia
  • Miliary tuberculosis
  • malignant histiocytosis
  • Complications
  • Worsening Continuous ill health
  • Death

20
Relevant investigations
  • Complete blood count, and ESR, reticulocyte
    count, combs 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.

21
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

22
Relevant investigations
  • Cell Markers e.g. using a panel of antibodies
    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

23
Relevant investigations
  • 7 Immunological Classification
  • Terminal deoxy nucleotidyl transferase
    demonstration in nucleus of B- and T lineage by
    means of a
  • aN antibody using.

24
Management
  • (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.

25
Drug treatment
  • 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. 12,15,18,21,24,27,3
    0,33.

26
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

27
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
    15mg. x 5 doses over 3 weeks
  • i.e. twice weekly

28
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.

29
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.

30
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.

31
  • Use either TAD or COAP as shown below
  • TAD
  • Cytarabine 100mg/ m2 (cont inf) d12 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

32
AML
  • Or COAP as shown below
  • Cyclophosphamide 650mg/m2 1V 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

33
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.

34
Thank you
  • For
  • Your
  • Attention

35
ACUTE MYELOID LEUKAEMIA
  • 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.

36
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

37
AML
  • M4 .Myelomonocytic with both granulocytic and
    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 gt 50
  • erythroblasts
  • M7 Megakaryoblastic

38
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 gt F

39
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 ?

40
PATHOPHYSIOLOGY
  • Suppress normal haemopoiesis
  • ?
  • result in replacement of normal elements.
  • ?
  • anaemia, infections bleeding complications.
  • - Primarily proliferate in BM

41
PATHOPHYSIOLOGY
  • circulate in the blood and infiltrate into other
  • tissues such as
  • Lymph nodes, skin, gum,
  • . Liver viscera, CNS.
  • . Spleen

42
PATHOPHYSIOLOGY
  • Growth. Advantages of Leukaemia cells
  • Mechanisms ? unknown
  • Postulates - GF production
  • GF Receptors.
  • . Factor Receptor coupling on normal versus
    Leukaemia cells may play a role
  • . Transforming genes or cellular oncogene
    expressed in leukaemia cells code for GF
    receptors

43
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 .

44
  • May involve a fundamental alteration of DNA
    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
    proto- oncogenes (insertional mutagenesis)
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