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LEUKEMIAS

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LEUKEMIAS Dr.Nazzal Bsoul Hematologist Al Bashir Hospital Bone marrow Bone marrow aspirate and biopsy: 1-Granulocytic hyperplasia. 2- Increase in ... – PowerPoint PPT presentation

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Title: LEUKEMIAS


1
LEUKEMIAS
  • Dr.Nazzal Bsoul
  • Hematologist
  • Al Bashir Hospital

2
Terminology
  • Leukos White
  • Aimia Blood
  • Leukemia--------Leukaemia ?
  • Hematology-----Haematology ?
  • Leukemoid reaction

3
Definition
  • Leukemia is a cancer of the blood or bone marrow
    characterized by abnormal proliferation of blood
    cells,usually WBCs(Leukocytes).
  • Acute leukemia rapid increase of immature blood
    cells.
  • Chronic leukemia excessive build up of
    relatively mature,but still abnormal blood cells.

4
Leukemoid Reaction
  • A leukemoid reaction describes a high
  • WBC count with neutrophilia,usually in
  • response to infection.
  • The WBC count may be as high as 50,000
  • /microL and can easily mimic CML or
  • AML.

5
Features Suggesting Leukemoid Reaction
  • Toxic granulation.
  • High LAP score.
  • Presence of an obvious cause for the
  • neutrophilia.

6
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7
Signs and Symptoms
  • Most of the signs and symptoms are due to
  • 1-Anemia.
  • 2-Leukopenia.
  • 3-Thrombocytopenia.
  • Bicytopenia,Pancytopenia.
  • All symptoms associated with leukemia
  • can be attributed to other diseases,
  • consequently,leukemia is always
  • diagnosed by laboratory investigations.

8
Causes
  • Leukemia,like other malignancies, results
  • from somatic mutations in the DNA.
  • Certain mutations produce leukemia by
  • activating oncogenes or deactivating
  • tumor suppressor genes.
  • These mutations may occur spontaneously
  • or as a result of exposure to
    radiation
  • or carcinogenic substances,and likely
  • to be influenced by genetic factors.

9
Causes-contd
  • Ionizing radiation
  • Viruses Human T-lymphotropic virus (HTLV-1)
  • Chemicals Benzene,chemotherapy.
  • Smoking slight increase in leukemia
  • incidence.
  • Genetic predisposition toward developing
  • leukemia Down syn.,Fanconi anemia

10
  • Acute Myeloid Leukemia

11
Definition
  • Acute myeloid leukemia (AML) acute
  • myelogenous leukemia,acute non-
  • lymphocytic leukemia.
  • AML consists of a group of relatively well-
  • defined hematopoietic neoplasms
  • involving precursor cells commited
  • to the myeloid line(WBCs,RBCs,PLTs)

12
Chracteristics
  • AML is characterized by a clonal proli-
  • feration of myeloid precursors with a
  • reduced capacity to differentiate into
  • mature cellular elements.
  • As a result,there is an accumulation of
  • leukemic blasts or other immature
  • forms in the BM,peripheral blood,and
  • other tissues with a variable
    reduction in
  • the production of normal
    RBCs,platelets,
  • and mature granulocytes.

13
Epidemiology
  • AML is the most common acute leukemia
  • in adults (80).
  • In USA 3-5 cases per 100 000 population.
  • In contrast AML accounts for less than
  • 10 of acute leukemia cases in
  • children less than 10 years of age.
  • The M/F ratio is approximately 53.

14
Epidemiology-contd
  • AML has been associated with following
  • 1-Environmental factors chemicals,
  • radiation,tobacco,and chemotherapy.
  • 2-Genetic abnormalities Down syndrome,
  • Fanconi anemia.
  • 3-Other benign hematological disorders
  • Paroxysmal nocturnal hemoglobinuria
  • 4-Malignant hematological disordersMDS,MPN

15
Classification
  • Multiple classification systems.
  • FAB classification
  • French-American-British Classification.
  • FAB Classification relies on morphologic,
  • cytochemical,and immunophenotyping
  • criteria to define 8 major subtypes
  • (M0-M7)

16
Clinical Presentation
  • Patients with AML present usually with
  • symptoms related to pancytopenia
  • 1-Anemia.
  • 2-Leukopenia with neutropenia.
  • 3-Thrombocytopenia.

17
Pathological Features
  • CBC and differential.
  • Blood film (smear).
  • Bone marrow examination BM aspirate
  • and trephine biopsy.
  • 1-Morphology.
  • 2-Immunephenotyping.
  • 3-Cytogenetics and molecular biology.

18
WBC Count in AML
  • WBC count in AML can be high,normal,or
  • low.
  • Median WBC count in AML is 15 000/uL.
  • 20 of patients have gt 100 000/uL
  • 25-40 of patients have lt5000/uL
  • 95 of patients have blast cells on blood
  • film.

19
Treatment
  • AML is usually treated with
  • 1-Chemotherapeutic agents.
  • 2-Bone marrow transplantation (BMT),
  • hematopoietic stem cell
    transplantation
  • (HSCT).
  • 3-Supportive treatment blood
    transfusion,
  • PLT transfusion,Granulocyte colony
  • stimulating factor (G-CSF),i.v
    fluids,
  • antibiotics.

20
Prognosis
  • The response to treatment and overall
  • survival of patients with AML are
  • heterogenous.
  • Prognostic factors are related to patient
  • and tumor characteristics
  • 1-Age
  • 2-Performance status
  • 3- Karyotype

21
Adverse Clinical Predictors
  • Advanced age.
  • Poor performance status.
  • History of exposure to cytostatic agents or
  • radiotherapy.(Therapy-related AML).
  • History of MDS or other hematological
  • diseases

22
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23
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24
  • Chronic Myeloid Leukemia (CML)

25
Terminology
  • Chronic myeloid leukemia (CML).
  • Chronic myelocytic leukemia.
  • Chronic myelogenous leukemia.
  • Chronic granulocytic leukemia (CGL).

26
Definition
  • CML is a myeloproliferative neoplasm
  • characterized by the dysregulated
    production
  • and uncontrolled proliferation of mature
  • and maturing granulocytes with fairly
  • normal differentiation.
  • CML is associated with the fusion of genes
  • BCR(on chromosome 22)and ABL1(on
  • chromosome 9), resulting in the
    BCR/ABL1
  • fusion gene.

27
  • This abnormal fusion gene (protein)
  • typically results from a reciprocal
  • translocation between chromosome
  • 9 and 22,t(922).(Philadelphia
  • chromosome)

28
Epidemiology
  • CML accounts for 15-20 of leukemias in
  • adults.
  • Annual incidence of 1-2 cases per 100,000
  • Median age at presentation is 60 years.
  • Exposure to ionizing radiation is the only
  • known risk factor.
  • The prevalence of CML is steadily
  • increasing due to ?.

29
Clinical manifestation
  • CML has a triphasic or biphasic course-
  • 1-Chronic phase 85 of pts.at dg.
  • 2-Accelerated phase WBC count is
  • more difficult to control.
  • 3-Blast crisis a condition resembling
  • acute leukemia (AML,ALL).

30
Clinical findings
  • Clinical findings at dg. vary among
  • reported series and also depend
  • upon the stage of the disease at dg.
  • 20-50 of patients are asymptomatic.
  • 50-80 of patients are symptomatic
  • Systemic symptoms(fatique,w.loss,
  • excessive sweating,bleeding due to
  • PLT dysfunction).

31
Clinical findings-contd
  • Abdominal symptomatology Lt.UQ
  • pain,early satiety,nausea,vomiting.
  • Tenderness over the lower sternum.
  • Other frequent findings include
  • Splenomegaly 48-76 of cases.
  • Anemia 45-62 of cases.
  • Leukocytosis WBC count above
  • 100,000/microL.
  • Thrombocytosis 15-34 of cases.

32
Peripheral blood
  • Leukocytosis median WBC count 100,000
  • /microL(range 12-1000/microL).
  • Anemia 45-60.Normochromic,normocyt.
  • Thrombocytosis above 600,000(15-30)
  • Blood filmall stages of maturation.
  • LAP score Low (Leukemoid reaction high
  • or N)
  • Absolute basophilia,eosinophilia,
  • monocytosis.

33
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34
Bone marrow
  • Bone marrow aspirate and biopsy
  • 1-Granulocytic hyperplasia.
  • 2- Increase in reticulin fibrosis and
  • vascularity.

35
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36
Genetics
  • Genetic testing for t(922)(q32q11,2)
  • Philadelphia chromosome.
  • BCR/ABL1 fusion gene
  • Fusion mRNA gene product
  • Conventional cytogenetic analysis (karyo-
  • typing)
  • Florescence in situ hybridization (FISH)
  • Reverse transcription PCR (RT-PCR).

37
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38
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39
Diagnosis
  • CML is suspected in a patient with some
  • of the findings mentioned above(syst.
  • complaints,early satiety,hepatospleno-
  • megaly,leukocytosis.)
  • Morphologic features in the blood and
  • BM.
  • Confirmed by genetic studies.

40
Differential diagnosis
  • Leukemoid reaction.
  • Juvenile myelomonocytic leukemia(JMML)
  • Chronic myelomonocytic leukemia(CMML)
  • Atypical CML.
  • Chronic eosinophilic leukemia.
  • Chronic neutrophilic leukemia.
  • Other myeloproliferative neoplasms.
  • Other Ph chromosome-posit.Malignancies.

41
Prognosis
  • The stage of disease at dg.is the strongest
  • single predictor of outcome in patients
  • with CML.
  • Scoring systems Sokal prognostic score4
  • clinical variables
  • 1-Spleen size
  • 2-Percent blasts.
  • 3-Age
  • 4-PLT count above 700,000/microL.

42
Treatment of CML
  • Available treatment options
  • 1-Allogeneic hematopoietic stem cell
  • transplantation (HSCT,BMT) curative
  • treatment option.
  • 2-Disease control without cure using
  • tyrosine kinase inhibitors (TKIs).
    3-Palliative therapy with cytotoxic agents
  • 4-Investigational therapies Farensyl
  • transferase inhibitors,dicitabine.

43
Choice of therapy
  • Factors influencing the choice of therapy
  • 1-Phase of the disease.
  • 2-Availability of a donor for HSCT.
  • 3-Patient age.
  • 4-Presence of co-morbidities.
  • 5-Response to treatment with TKIs.

44
Choice of therapy
  • Factors influencing the choice of therapy
  • 1-Phase of the disease.
  • 2-Availability of a donor for HSCT.
  • 3-Patient age.
  • 4-Presence of co-morbidities.
  • 5-Response to treatment with TKIs.

45
Tyrosine Kinase Inhibitors (TKIs)
  • TKIs target the active tyrosine kinase
  • implicated in the pathogenesis of CML.
  • 1-First-generation oral TKIs
  • Imatinib (Glivec,Cemivil).
  • 2-Second-generation TKIs
  • Nilotinib (Tasigna),Dasatinib
    .
  • Although TKIs do not cure CML,these
  • agents are able to achieve long-term
  • control of the disease.

46
  • THANK YOU
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