CML

Question 1

definition of CML

Answer 1

malignant clonal disease

characterised by proliferation of granulocyte precursers in the bone marrow and blood

distinguised bt AML by its slower progression

myeloproliferative disorder

Question 2

aetiology of CML

Answer 2

malignant proliferation of stem cells with characteristic (95% cases) t(9;22) translocation = philadelphia chromosome

variants include Ph-negative CML, chronic neutrophilic leukaemia and eosinophilic leukaemia

Question 3

pathoogy of CML

Answer 3

the Ph chromosome = fusion of the genes BCR and ABL - hybrid chromosome comprising reciprocal translocation between long arm of 9 and long 22 = BCR-ABL on 22

= transcription fo a 210-kDa protein (BCR-ABL) with enhanced tyrosine kinase activity that drives cell replication

present in >80% of those with CML = better prognosis

Question 4

3 phases of CML

Answer 4

relatively stable chronic phase of variable duration (average of 4-6yr) - few if any sx

transforms to accelarated phase (3-9mo) - increased sx, spleen size, difficulty in controlling counts

then an acute leukaemia phase (blast transformation)

Question 5

epidemioloy of CML

Answer 5

incidence increases with age

mean 40-60yrs

males

accounts for 15% of leukaemias

Question 6

sx of CML

Answer 6

asymptomatic in 40-50% and is diagnosed on the blood count

hypermetabolic sx - weight loss, malaise, sweating, fever

bone marrow failure sx - lethargy, dyspnoea, easy bruising, epistaxis (infection is rare)

abdominal discomfort, early satiety

occaisionally - gout or hyperviscosity sx (visual disturbane, headache, priapism) - due tio purine break down

bleeding - platelet dysfunction

abdo discomfort - splenic enlargement

may present during blast crisis with sx of AML or ALL

Question 7

signs of CML

Answer 7

splenomegaly - most common physical finding (90%)

hepatomegaly

signs of bone marrow failure - pallor, cardiac flow murmur, bleeding or echymoses

Question 8

Ix for CML

Answer 8

blood

• FVC - very high WCC, low Hb, high basophils/eosinophils/neutrophils/monocytes
• high plt but may be normal or low
• high uric acid
• low neutrophil alkphos
• high vit B12 and B12 binding protein (transcobalamin 1)

blood film - immature granulocytes in peripheral blood

bone marrow aspirate or biopsy - hypercellular with raised myeloid-erythroid ratio

cytogenics to demonstrate Ph chromosome