Jihad al- Gadeeb Medicle Intern

CHRONIC MYELOID LEUKAEMIA

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, eosinophils.

• 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.

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