Chronic Myeloid Leukaemia

also known as Chronic Granulocytic Leukaemia

• Forms 20% leukaemias

• Female 4x as likely as men

• Peak age 40-50 (may occur in children)

Clinical Features

• fatigue

• weight loss

• abdominal pain / splenomegaly

• anaemia

• hyperviscosity effects

  • thrombosis

• gout

• fever

• sweating

Investigations

• FBC

• Blood film

  • left-sided shift (cells in circulation more immature than might be expected)

• Bone marrow aspirate / trephine

• Cytogenetics

  • characterised by Philadelphia chromosome

  • others 22q-, il&, +8, +19, additional Philadelphia chromosomes indicate transformation into accelerated phase

Aetiology

• increased risk after radiation exposure

• stem cell disorder

Course

• Chronic phase - lasts 1 - 10 years (median 3.5)

• Accelerated phase - months

Features of accelerated phase

• Rising WCC, refractory to conventional chemotherapy

• >12 % peripheral blood blasts

• >20% bone marrow blasts and promyelocytes

• anaemia

• thrombocytopenia

• Platelets >1000

• New chromosomal abnormalities

• Persisting / increasing splenomegaly

• bone marrow failure with myelofibrosis

Treatment

• Objective to cure or prolong survival

  • control counts

  • get Philadelphia / BCR-ABL negativity

• Allogenic Bone Marrow Transplant

  • only chance of cure

  • problems

    • few people eligible

    • 40-60% procedure related mortality (will be less with reduced intensity conditioning)

    • when to do

    • long term morbidity

• Hydroxyurea

  • controls counts

  • alleviates symptoms

  • may make Philadelphia chromosome  negative / very small numbers of Ph +ve cells

• Busulphan

• Ara-C

  • better outcomes but needs SC injections

• Interferon

  • controls counts

  • effects disease at molecular level - may render Philadelphia negative

  • needed high doses so intolerable to some

• Signal Transduction Inhibitors

  • Gleevec / STI571

  • inhibits the BCR-ABL tyrosine kinase

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