haematology,

Chronic Myeloid Leukaemia (CML)

Sep 09, 2020

Mnemonic

Children and Middle aged people are Able to have a blast in Philadelphia

  • CML
  • Affects Middle and children aged (usual age 13-40)
  • BCR-ABL (9:22) aka Philadelphia chromosome translocation
  • Blast crisis and blast transformation (i.e. leukaemia)

Introduction

  • Uncontrolled clonal proliferation of myeloid cells
  • A type of myeloprofliferative disorder (myelo = myeloid, proliferative= increase in number, see box)
  • Age 40-60 yrs
  • Philadelphia chromosome i.e. a hybrid chromosome due to translocation of ch9 onto ch22 → BCR/ABL gene affected → codes for tyrosine kinase

Signs and symptoms

  • Symptoms (chronic and insidious)
    • ↓weight, tiredness, fever, sweats
    • abdominal discomfort (splenic enlargement)
  • Signs
    • Splenomegaly (>75%)—often massive
    • Hepatomegaly, anaemia, bruising

Investigation

  • Blood count ↑↑wbc (often >100×10^9/L) with whole spectrum of myeloid cells, ie ↑ neutrophils, monocytes, basophils, eosinophils

    • ↓Hb or ↔, platelets variable
  • Biopsy
    • Bone marrow hypercellular
  • Cytogenetic
    • Philadelphia chromosome

Natural history (3 phase)

  • Chronic phase: lasting months or years with limited symptoms
  • Accelerated phase: , spleen size, and difficulty in controlling counts; increasing symptoms
  • Blast transformation: with features of acute leukaemia ± death

Management

  • Tyrosin kinase inhibitor (TKI) e.g. Imatinib (1st generation), Dasatinib (2nd generation)
  • Stem cell transplantation