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CHRONIC MYELOID
   LEUKAEMIA

  Jihad al- Gadeeb
   Medicle Intern
CML
• Chronic myelogenous leukemia (CML), also
  known as chronic myeloid leukemia, is a
  myeloproliferative disorder characterized by
  increased proliferation of the granulocytic cell
  line. Consequently, the peripheral blood cell
  profile shows an increased number of
  granulocytes and their immature precursors,
  including occasional blast cells.
INCIDENCE

• 15% of leukaemias.
• It occurs most often between 40–
  60yrs
• slight male predominance
Phladiphia chromosome



• Present in >80% of those with CML. It is a
  hybrid chromosome comprising reciprocal
  translocation between the long arm of
  chromosome 9 and the long arm of
  chromosome 22—t(9;22) forming a fusion
  gene BCR/ABL on chromosome 22, which
  has tyrosine kinase activity
causes

• The initiating factor of CML is still unknown,
  but exposure to ionizing radiation
• increased prevalence among survivors of the
  atomic bombing of Hiroshima and Nagasaki.
• Radiotherapy for a cancer in the past
• benzene
CML progresses through 3 phases


• Chronic phase
• Accelerated phase
• Blast phase.
Chronic phase


• Mature cells proliferat
• its response to the treatment and easilly
  controlled
The accelerated phase


• Additional cytogenetic abnormalities occur
• Diesease controle becomes more difficult
The blast phase


• in the blast phase, immature cells rapidly
  proliferat
• The disease transform from chronic to acut
  leukemia which relitivelly not response to the
  treatment
•
• Approximately 85% of patients are
  diagnosed in the chronic phase and then
  progress to the accelerated and blast phases
  after 3-5 years.
• The diagnosis of CML is based on the
  histopathologic findings in the peripheral
  blood and the Philadelphia chromosome in
  bone marrow cells
Clinical picture

• Clinical picture

•   Low-grade fever
•    excessive sweating hypermetabolism.
•    fatigue
•   weight loss
•   Loss of energy
•    decreased exercise tolerance

• Left upper quadrant abdominal pain described as
  "gripping"
• In some patients who present in the
  accelerated, or acute, leukemia phase of the
  disease (skipping the chronic phase), bleeding,
  petechiae, and ecchymoses may be the
  prominent symptoms
• Bone pain and fever, as well as an increase in
  bone marrow fibrosis

• may be features of gout
•   Investigation
•   CBC with differential
•    peripheral blood smear
•    bone marrow analysis
•    US using for liver/spleen
• WBC ↑↑ (often >100 × 109/L) with whole
  spectrum of myeloid cells ie
  ↑neutrophils, myelocytes, basophils, eosinop
  hils.
• Hb↓ or normal,
• platelets variable.
• Urate↑,

• B12↑
• Bone marrow is hypercellular. Ph found on
  cytogenetic analysis of blood or bone marrow
Treatment

• Chronic phase:
• Hydroxyurea or interferon-α, with allopurinol

• Specific treatment:
• Imatinib and Dasatinib (tyrosine kinase inhibitors) act
  as inhibitors ofBCR-ABL.

• Stem cell transplantation
• :Allogeneic or autogenous.
• Hydroxyurea
• may still be used in patients intolerant of
  imatinib


• Dasatinib
• may have a role in imatinib-resistant blast
  crises.
• Hydroxyurea
• may still be used in patients intolerant of
  imatinib


• Dasatinib
• may have a role in imatinib-resistant blast
  crises.
 Chronic Myeloid Leukemia

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Chronic Myeloid Leukemia

  • 1. CHRONIC MYELOID LEUKAEMIA Jihad al- Gadeeb Medicle Intern
  • 2. CML • Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a myeloproliferative disorder characterized by increased proliferation of the granulocytic cell line. Consequently, the peripheral blood cell profile shows an increased number of granulocytes and their immature precursors, including occasional blast cells.
  • 3. INCIDENCE • 15% of leukaemias. • It occurs most often between 40– 60yrs • slight male predominance
  • 4. Phladiphia chromosome • Present in >80% of those with CML. It is a hybrid chromosome comprising reciprocal translocation between the long arm of chromosome 9 and the long arm of chromosome 22—t(9;22) forming a fusion gene BCR/ABL on chromosome 22, which has tyrosine kinase activity
  • 5.
  • 6. causes • The initiating factor of CML is still unknown, but exposure to ionizing radiation • increased prevalence among survivors of the atomic bombing of Hiroshima and Nagasaki. • Radiotherapy for a cancer in the past • benzene
  • 7. CML progresses through 3 phases • Chronic phase • Accelerated phase • Blast phase.
  • 8. Chronic phase • Mature cells proliferat • its response to the treatment and easilly controlled
  • 9. The accelerated phase • Additional cytogenetic abnormalities occur • Diesease controle becomes more difficult
  • 10. The blast phase • in the blast phase, immature cells rapidly proliferat • The disease transform from chronic to acut leukemia which relitivelly not response to the treatment •
  • 11.
  • 12. • Approximately 85% of patients are diagnosed in the chronic phase and then progress to the accelerated and blast phases after 3-5 years.
  • 13. • The diagnosis of CML is based on the histopathologic findings in the peripheral blood and the Philadelphia chromosome in bone marrow cells
  • 14.
  • 15.
  • 16. Clinical picture • Clinical picture • Low-grade fever • excessive sweating hypermetabolism. • fatigue • weight loss • Loss of energy • decreased exercise tolerance • Left upper quadrant abdominal pain described as "gripping"
  • 17. • In some patients who present in the accelerated, or acute, leukemia phase of the disease (skipping the chronic phase), bleeding, petechiae, and ecchymoses may be the prominent symptoms
  • 18. • Bone pain and fever, as well as an increase in bone marrow fibrosis • may be features of gout
  • 19. Investigation • CBC with differential • peripheral blood smear • bone marrow analysis • US using for liver/spleen
  • 20. • WBC ↑↑ (often >100 × 109/L) with whole spectrum of myeloid cells ie ↑neutrophils, myelocytes, basophils, eosinop hils. • Hb↓ or normal, • platelets variable. • Urate↑, • B12↑
  • 21.
  • 22. • Bone marrow is hypercellular. Ph found on cytogenetic analysis of blood or bone marrow
  • 23. Treatment • Chronic phase: • Hydroxyurea or interferon-α, with allopurinol • Specific treatment: • Imatinib and Dasatinib (tyrosine kinase inhibitors) act as inhibitors ofBCR-ABL. • Stem cell transplantation • :Allogeneic or autogenous.
  • 24. • Hydroxyurea • may still be used in patients intolerant of imatinib • Dasatinib • may have a role in imatinib-resistant blast crises.
  • 25. • Hydroxyurea • may still be used in patients intolerant of imatinib • Dasatinib • may have a role in imatinib-resistant blast crises.