The Acute Leukaemias - PowerPoint PPT Presentation

Loading...

PPT – The Acute Leukaemias PowerPoint presentation | free to view - id: 10b68e-MWQyZ



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

The Acute Leukaemias

Description:

Is the proliferation and accumulation of abnormal white ... Common Karyotype Abnormalities. AML - t(8;21) m2, better prognosis. t(15;17) m3, better prognosis ... – PowerPoint PPT presentation

Number of Views:334
Avg rating:3.0/5.0
Slides: 42
Provided by: comput124
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: The Acute Leukaemias


1
The Acute Leukaemias
  • Moira Stephens
  • Clinical Nurse Specialist
  • Haemato-oncology
  • Royal Marsden Hospital, UK

2
Leukaemia
  • Is the proliferation and accumulation of abnormal
    white cells within the bone marrow
  • The white cells may cause a crowding out
    phenomena causing -
  • Bone marrow failure
  • Cells spilling into the peripheral blood and may
    infiltrate other organs

3
(No Transcript)
4
Leukaemia
  • Acute - Immature cell lines affected
  • Myeloid or Lymphoid cell lines
  • Chronic - Mature cell lines affected
  • Myeloid or Lymphoid cell lines

5
Diagnostics 1 - Morphology
Normal Bone Marrow
6
Diagnostics 2-Immunophenotyping
  • Identification of cell surface proteins by
    reactivity with monoclonal antibodies of known
    specificity
  • Common Diagnostic profiles -
  • AML - CD 13, CD33, CD34, CD14 ve
  • cALL - CD10 ve, TdTve
  • T-ALL - CD3, CD7, TdT ve
  • B-ALL - CD10, CD19, surface Ig ve
  • CLL - CD5, CD19, CD23, weak surface Ig ve

7
Diagnostics 3 -Cytogenetics
  • Acquired chromosomal abnormalities are common in
    haematological malignancies (determination of
    patterns - karyotyping)
  • normal cell- (46 chromosomes, 22 pairs xx or
    xy. 2 arms meet at centromere - short arm p, long
    arm q, usually only visible during condensation
    at metaphase, Fluorescence In Situ Hybridisation,
    cell cultures stimulants)

8
Diagnostics 3aCommon Karyotype Abnormalities
  • AML - t(821) m2, better prognosis
  • t(1517) m3, better prognosis
  • inv 16 m4, better prognosis
  • -5, -7 Complex abnormalities have poor
    prognosis
  • ALL t(922) Philadelphia chromosome creates
    bcr-abl gene
  • t(922) poor prognosis
  • t(411) poor prognosis
  • hyperdiploidy- increase in total
    chromosome no. - good prognosis
  • Hypodiploidy - decrease in total chromosomes
    - bad prognosis
  • B-ALL - (t814) bad prognosis

9
Acute Myeloid Leukaemia
  • Malignant tumour of haemopoietic precursor cells
    of non-lymphoid lineage.
  • Incidence - 1/10,000 annually
  • Increasing frequency with age
  • (median 60yrs)
  • Cause unclear - assoc. radiation exposure,
    benzene, alkylating agents, hereditary
    predisposition in Downs, Fanconis and Blooms
    Klinfelters syndromes

10
AML - Morphological Classification (FAB)
  • M0 - Undifferentiated
  • M1 - Early myeloblastic
  • M2 - Late myeloblastic
  • M3 - Promyelocytic
  • M4 - Myelomonocytic
  • M5 - Monoblastic
  • M6 - Erythroleukaemic
  • M7 - Megakaryoblastic

11
Pluripotent stem cell
Multipoint Myeloid stem cell
Lymphoid stem cell common NULL
Pre-T cell
Pre-B cell
CFU-Gemm
T.Lymphoblast T ALL
B.Lymphoblast B ALL
CFU-E
CFU-MEG
CFU-GM
CFU-G
CFU-M
Erythroblast M6
Megakaryoblast M7
Myeloblast M1, M2
Prolymphocyte B PLL
Prolymphocyte T PLL
Monoblast M5
Promegakayocyte
Promyelocyte M3
Promonocyte
T Cell T CLL, Sezary
Reticulocyte
B Cell B CLL. HCL
Megakaryocyte
Neutrophilic Monocyte M4
Plasma Cell Myeloma, PCL
Erythrocyte
Thrombocyte
Monocyte
Macrophage
Polymorph
12
WHO AML Classification
  • Acute Myeloid Leukaemia with recurrent genetic
    abnormalities
  • Acute Myeloid Leukaemia with multilineage
    dysplasia
  • Acute Myeloid Leukaemia and myelodisplastic
    syndromes therapy related
  • Acute Myeloid Leukaemia not otherwise categorised
  • Acute Leukaemias of ambiguous lineage

13
Acute Myeloid Leukaemia with recurrent genetic
abnormalities
  • AML with t(821) (q22q22) (AML1/ETO)
  • AML with abnormal bone marrow eosinophils inv
    (16)(p13q22) or t(1616)(p13q22)
  • PML with t(1517)(q22q12) and variants
  • AML with 11q23 abnormalities

14
Acute Myeloid Leukaemia with multilineage
dysplasia
  • Following myelodysplastic syndrome or
    myeloproliferative disorder
  • Without antecedent myelodysplastic syndrome

15
Acute Myeloid Leukaemia and myelodisplastic
syndromes therapy related
  • Alkylating agent related (and/or RT)
  • Topoisomerase type 2 inhibitor related
    (Etoposide/Tenoposide)

16
Acute Myeloid Leukaemia not otherwise
categorised
  • AML minimally differentiated M0
  • AML without maturation M1
  • AML with maturation M2
  • Acute myelomonocytic leukaemia M4
  • Acute monoblastic (M5a) and
  • myelomonocytic leukaemia (M5b)
  • Acute erythroid leukaemia M6
  • Acute megakaryoblastic leukaemia M7
  • Acute basophilic leukaemia
  • Acute panmyelosis with myelofibrosis acute
    myelofibrosis/sclerosis
  • Myeloid Sarcoma chloroma/granulocytic
    sarcoma/extramedullary myeloid tumour

17
Acute Leukaemias of ambiguous lineage
  • Undifferentiated acute leukaemia no expression
  • Bilineal acute leukaemia 2 groups
  • Biphenotypic acute leukaemia co-express

18
AML - diagnosis
  • Morphology -
  • Immunophenotyping - (CD surface protein markers)
  • useful in M0, 4,5,6,7
  • Cytogenetics -
  • important in detecting deletions translocations

19
AML m1 blast
20
AML m3 auer rods
21
AML - Clinical features
  • Acute presentation common often critically ill
  • Fever, malaise, anaemic symptoms, infections
  • Bleeding, purpura, spontaneous bruising
  • Leucostatic signs
  • Soft tissue infiltration

22
AML m4 - Gum Hypertrophy
23
AML - investigations
  • FBC and blood film
  • WBC, diff, plats RBC
  • Bone marrow -asp biopsy -
  • hypercellular with proliferation of blasts (gt
    30)
  • Other- ? LP, ? CxR, ? CT/MRI

24
AML - Treatment
  • Stabilise -
  • Leucostasis , Haemorrhage, Sepsis
  • Psychological support
  • Hydration allopurinol / rasburicase
  • RBC platelet support

25
AML -Specific treatment (non m3)
  • Age and co-morbidity , trials
  • 4 5 courses
  • Induction consolidation
  • Anthracycline Cytosine

26
AML M3
  • MRC approach 4 courses
  • ADE (310) ATRA to CR
  • ADE (38)
  • MACE or MACE Mylotarg
  • MiDAC
  • Spanish approach -
  • Idarubicin 12mg/m2 ATRA to CR
  • Idarubicin 7mg/m2 ATRA
  • Mitoxantrone ATRA /- Myelotarg
  • Idarubicin 12mg/m2
  • Maintenance MTX weekly,6MP ATRA 15 days for 3
    monthly for 2 years

27
FLAG-Ida
  • Fludarabine 30mg/m2 od IV (1/2 hr inf)
  • Days 2 6 ( T 0)
  • Cytosine 2gm/m2 od infusion
  • days 2 6 (T4)
  • Idarubicin 10mg/m2 od IV days 4,5,6
  • G-CSF (lenograstin 263ug) s.c. od
  • days 1 7
  • Bone marrow between days 18 - 21

28
ADE (1035) (835)
  • Cytosine 100mg/m2 12 hourly IV push days 1 10
    (8)
  • Daunorubicin 50mg/m2 IV push od
  • days 1,3,5
  • Etoposide 100mg/m2 od IV infusion
  • days 1 5
  • Bone marrow day 18 - 21

29
DA (310) (38)
  • Daunorubicin 50mg/m2 IV push
  • days 1,3,5
  • Cytosine 100mg/m2 12 hourly by IV push on days 1
    -10
  • Bone marrow day 18 - 21

30
Consolidation treatment
  • Course 3
  • MACE /- myelotarg
  • Ara C (1.5 OR 3 gm/M2) /- myelotarg
  • Standard allograft
  • MACE
  • Course 4
  • MiDAC
  • Ara C 1.5 or 3gm/m2
  • Mini allograft
  • Course 5
  • Ara C 1.5gm/m2
  • No further treatment

31
Acute Lymphoblastic Leukaemia
  • Malignant tumour of haemopoetic precursor cells
    of lymphoid lineage
  • Incidence - commonest malignancy in childhood,
    majority of cases 2 - 10yrs, rare in adults
    170,000 annually
  • slight peak in old age
  • Cause unclear, as AML proximity to Radon and
    Power lines postulated

32
ALL Classification
  • Morphology (FAB)
  • L1 - Commonest, small homogenous blasts, single
    nucleolus
  • L2 - Blasts larger, more pleomorphic and
    multinucleolate
  • L3 - Blasts larger, basophilic and vacuoles
    (assoc with B cell phenotype)

33
WHO ALL Classification
  • Precurser B cell acute lymphoblastic leukaemia
  • Precurser T cell acute lymphoblastic leukaemia
  • L1 and L2
  • Burkitt Leukaemia L3

34
Pluripotent stem cell
Multipoint Myeloid stem cell
Lymphoid stem cell common NULL
Pre-T cell
Pre-B cell
CFU-Gemm
T.Lymphoblast T ALL
B.Lymphoblast B ALL
CFU-E
CFU-MEG
CFU-GM
CFU-G
CFU-M
Erythroblast M6
Megakaryoblast M7
Myeloblast M1, M2
Prolymphocyte B PLL
Prolymphocyte T PLL
Monoblast M5
Promegakayocyte
Promyelocyte M3
Promonocyte
T Cell T CLL, Sezary
Reticulocyte
B Cell B CLL. HCL
Neutrophilic Monocyte M4
Megakaryocyte
Plasma Cell Myeloma, PCL
Erythrocyte
Thrombocyte
Polymorph
Monocyte
Macrophage
35
ALL Lymphoblasts
36
ALL - Classification
  • Immunophenotyping - lymphocyte maturation markers
    distinguish early or null from pre-Bcell or
    common ALL
  • lt 10 T cell lineage
  • lt 5 B cell lineage
  • Cytogenetics - 10 -20 Ph ve (922)

37
ALL - Clinical features
  • Malaise, sweats, wt. loss, anorexia
  • Infections, bleeding, anaemia
  • Leucostatic signs
  • Widespread lymphadanopathy, mild/mod
    splenomegaly/hepatomegaly/orchidomegaly
  • CNS signs
  • SVCO

38
ALL - Investigations
  • FBC and blood film -
  • wbc (may be low), blasts on film
  • Hb platelets often low
  • Bone marrow -asp biopsy
  • heavy infiltration of blasts
  • FISH (BCR-ABL)
  • Other- LP, CxR, CT

39
ALL - Treatment
  • Stabilise -
  • Leucostasis , Haemorrhage, Sepsis
  • LP if meningism
  • Psychological support
  • Hydration allopurinol/rasburicase
  • RBC platelet support

40
ALL - Specific treatment
  • UKALL XII (PH negative)
  • Induction
  • Phase 1 days 1 28
  • Daunorubicin vincristine days 1,8,15
  • Prednisone days 1-28
  • Asparaginase days17-28
  • mtx IT Bone marrow d24)
  • Phase 2 starts on day 29 (or wbc gt3.0)
  • Cyclophosphamide days 1,15 29
  • Cytosine days 1-4, 8-11,15-18, 22-25
  • 6mp od days 1-28
  • Intrathecal MTX days -1,7,14,21
  • Special considerations thrombophilia, PCP,
    fungal infection

41
ALL - Specific treatment
  • UKALL XII (PH negative)
  • Intensification
  • Methotrexate 3gm/m2 days 1,8 22 FA rescue
  • then Allograft or autograft or cycles 1 -4
    consolidation maintenance for 1 year
  • CNS prophylaxis
  • Intrathecal MTX
  • Cranial RT (2,400 gray 12 )
  • Intrathecal cytosine x 4 weekly with RT then 1
    dose 3 monthly during maintenance (1 year)
  • If for BMT no RT, 1 extra MTX
About PowerShow.com