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    CML

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    jourey08
    Chronic myelogenous leukemia (CML) is a type of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow. It results from a specific genetic mutation that produces the Philadelphia chromosome. The diagnosis of CML involves blood tests, bone marrow biopsy, and genetic testing to detect the Philadelphia chromosome and the associated BCR-ABL gene. Treatment of CML involves the use of tyrosine kinase inhibitors such as imatinib to target the abnormal BCR-ABL protein. The goals of treatment are hematologic, cytogenetic and molecular remission to suppress the disease. Prognosis depends on factors like time to remission and response to therapy.

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    CML

    Uploaded by

    jourey08
    167 views28 pages
    Chronic myelogenous leukemia (CML) is a type of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow. It results from a specific genetic mutation that produces the Philadelphia chromosome. The diagnosis of CML involves blood tests, bone marrow biopsy, and genetic testing to detect the Philadelphia chromosome and the associated BCR-ABL gene. Treatment of CML involves the use of tyrosine kinase inhibitors such as imatinib to target the abnormal BCR-ABL protein. The goals of treatment are hematologic, cytogenetic and molecular remission to suppress the disease. Prognosis depends on factors like time to remission and response to therapy.

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    CML

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    Chronic myelogenous leukemia (CML) is a type of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow. It results from a specific genetic mutation that produces the Philadelphia chromosome. The diagnosis of CML involves blood tests, bone marrow biopsy, and genetic testing to detect the Philadelphia chromosome and the associated BCR-ABL gene. Treatment of CML involves the use of tyrosine kinase inhibitors such as imatinib to target the abnormal BCR-ABL protein. The goals of treatment are hematologic, cytogenetic and molecular remission to suppress the disease. Prognosis depends on factors like time to remission and response to therapy.

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    167 views28 pages

    CML

    Uploaded by

    jourey08
    Chronic myelogenous leukemia (CML) is a type of leukemia characterized by the increased and unregulated growth of myeloid cells in the bone marrow. It results from a specific genetic mutation that produces the Philadelphia chromosome. The diagnosis of CML involves blood tests, bone marrow biopsy, and genetic testing to detect the Philadelphia chromosome and the associated BCR-ABL gene. Treatment of CML involves the use of tyrosine kinase inhibitors such as imatinib to target the abnormal BCR-ABL protein. The goals of treatment are hematologic, cytogenetic and molecular remission to suppress the disease. Prognosis depends on factors like time to remission and response to therapy.

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    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    of 28

    Sahyuddin

    Div. of Hematology & Medical Oncology


    Dept.of Internal Medicine, Medical Faculty
    Hasanuddin University
    Contents

    1 What is CML ?

    2 How is the pathophysiology of CML ?

    3 How to diagnosis CML ?

    4 How to manage patient with CML ?


    I. Chronic Myelogenous Leukemia (CML)

    increased proliferation of granulocytic cell

    CML without the loss of their capacity to diff.

    increased number of granulocytes


    I. Chronic Myelogenous Leukemia (CML)

    Chronic Myelogenous Leukemia ( CML )


    - Belongs to Myeloproliferative Disorders
    - Adult & elderly
    - Relatively slow clinical progression
    - Relatively better live expectancy than
    acute leukemia.
    I. Chronic Myelogenous Leukemia (CML)

    few cancers known to be caused by


    a single, specific genetic mutation.

    CML
    > 90% a cytogenetic aberration
    Ph chromosome
    I. Chronic Myelogenous Leukemia (CML)
    2. Accelerated phase :
    1.Chronic stable - Blasts 10-19% of wBC
    phase (CP): in peripheral & BM
    - blast < 10% in - Persistent
    the blood & BM thrombocytopenia
    - 85% pts dx/ in CP
    CML (< 100 109/L)
    (WHO) - persistent
    - Progres to AP & BP thrombocytosis
    after 3-5years (> 1000 109/L)
    - Increasing white blood
    cells & spleen size

    3. Blast crisis :
    - Blasts 20% of peripheral blood WBC or BM
    - Extramedullary blast proliferation
    - Large foci or clusters of blasts on bone marrow
    biopsy
    II. Etiology of CML :

    Not clear yet.


    - Cytotoxic drugs ?
    - Viruses ?
    - Radiation ?
    - Pollutants ?
    III. Pathogenesis of CML :

    Majority : Philadelphia chromosome (+)


    t (9:22) : resiprocal transversion of genetic
    material from chrom 9 to 22 (vv)
    new abnormal protein
    initiating abnormal proliferation of
    myeloid cells in bone-marrow CML.
    III. Pathophysiology
    Three-hit model of leukemogenesis

    Gain of function mutations


    of tyrosine kinases Loss of Apoptosis

    eg. FLT3, c-KIT mutations eg.:


    N- & K-RAS mutations
    BCR-ABL Bcl-2 over expression
    TEL-PDGFbR

    enhanced Normally Suppression


    proliferation + differentiation + apoptosis

    Chronic
    Leukemia
    III. Diagnosis of CML

    Physic
    Hemato

    Anamnesis CML

    Cytogen

    BCR-ABL
    Trias CML

    Splenomegali

    ADT : Pasar Malam Diagnosis CML

    Pemeriksan BCR-ABL
    Targeting terapi (TKI) :
    - Imatinip mesylate (Glivec)
    - Nilotinib (Tasigna)
    - Dasatinib
    III. The Diagnosis of CML +
    III. The Diagnosis of CML +
    III.Diagnosis of CML
    III. Diagnosis of CML

    CP AP BP
    III. Diagnosis of CML

    Cytogenetic
    III. Diagnosis of CML

    BCR-ABL
    IV. Management of CML

    The goals of treatment of CML

    1 2 3
    1.Hemato 2.Cytogen 3. Molecular
    remission remission remission
    (normal (normal (negative of
    complete chromosome) polymerase
    bloodcell , chain reaction
    count (CBC), (PCR) &
    negative of the
    mutational
    BCR/ABL
    mRNA)
    IV. Management of CML

    1. Cytoreduksi Agents

    2. Tyrosine kinase inhibitors

    3. Leucopharesis

    4. Transplantation
    IV. Management of CML

    Historis Terapi CML


    1. Cytoreduksi Agents :
    Th 1959 : Busulfan (Myleran)
    Th 1969 : Hydroxyurea fase lekositosis atau
    trombositosis.
    Th 1990 an : Interferon- (IFN) gold standard sampai
    diperkenalkannya Tyrosine Kinase Inhibitors (TKI)
    2. Tyrosine kinase Inhibitors (TKI)
    Imatinib (first TKI & gold standard /terapi lini pertama)
    TKI generasi ke 2 : Nilotinib & Dasatinib
    ( approved sbg lini kedua, kemudian juga utk lini pertama )
    IV. The Management of CML
    IV. Management of CML
    IV. Management of CML

    Leucopharesis:

    1. Severe leukositosis

    2. Complication (leukostasis)
    IV. Management of CML

    Splenectomy and splenic irradiation :


    patients with large and painful spleens,
    usually in the late phase of CML.

    splenectomy is associated with high perioperative


    morbidity and mortality rates because of bleeding
    or thrombotic complications.
    IV. Management of CML

    New technic :
    Peripheral Blood Stem-cell
    Transplantation ( PBSCT )
    Advantages :
    - no need operating theatre
    - relatively simple & easy procedure
    - low cost
    - most ideally procedure (?)
    V. Prognosis

    Prognosis depend on clinical & lab. Factor

    Prognosis depend on therapy associated


    factors:

    1. Time to hematology remission


    2. Duration of remission
    3. Total dose of chemotherapy
    4. Suppression of Ph-cell

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