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