Chronic Myeloid leukaemia

• Chronic myeloid leukaemia (CML) is a clonal myeloproliferative neoplasm characterised by abnormal clonal expansion of cells of the myeloid lineage.
• The condition is characterised genetically by the Philadelphia (Ph) chromosome, an abnormal chromosome 22 that results in a constitutively activated tyrosine kinase.
• CML often presents with non-specific symptoms like fatigue, weight loss and night sweats
• Around 20-40% are asymptomatic and picked up incidentally during investigations (FBC) for other reasons
• Splenomegaly is common, seen in at least 40- 50% of patients at diagnosis 
• Common symptoms on presentation:

  • 20-40% are asymptomatic
  • Splenomegaly - abdominal discomfort and early satiety
  • Fatigue
  • weight loss
  • Night sweats
• Features indicative of tissue infiltration (lymphadenopathy and bone pain) are rare and usually only seen in advanced disease
• CML tends to follow three phases: chronic, accelerated and blast crisis.
• Chronic phase:

  • vast majority of patients present in this phase
  • Non-specific clinical features
  • Phase tends to last 3-5 years
• Accelerated phase:

  • Symptoms and features become more apparent and severe
  • Increased blasts in the blood or marrow 15-29%
• Blood tests:

  • WCC elevated - specifically neutrophils
  • Raised basophils
  • Raised eosinophils
  • Anaemia and low platelets often seen
• Immature and mature myeloid cells are seen in CML. The proportion of blasts and basophils help to categorise the phase of disease.
• Blast crisis:

  • Resembles an acute leukaemia with the rapid expansion of blasts
  • Blasts in blood or marrow >30%
  • Extramedullary blast proliferation apart from the spleen
• Tyrosine kinase inhibitors: these drugs have completely transformed the management of CML. They directly inhibit tyrosine kinase - blocking the enzyme created by the BCR-ABL1 fusion gene
• Typical symptoms if present:

  • Upper abdominal pain due to hepatosplenomegaly
  • Poor appetite - splenomegaly
  • Low grade fever or night sweats
  • Gout
  • Recurrent infections
  • SOB and fatigue - anaemia
  • Easy bruising, petechiae, bleeding - low platelets
• Relevant laboratory investigations include:

  • Full blood count: leucocytosis, increased numbers of eosinophils and basophils, increased granulocytes, anaemia (normocytic/normochromic)
  • U&E: usually normal, useful for a baseline prior to treatment
  • Lactate dehydrogenase: may be raised
  • Urate: may be raised due to high cell turnover
• Methods for identifying the Philadelphia chromosome include FISH (fluorescent in-situ hybridisation) and PCR for the BCR-ABL gene.
• Tyrosine kinase inhibitors target BCR-ABL, blocking the ability of the gene to phosphorylate a tyrosine. This inhibits the proliferation of malignant cells.

  First line = Imatinib
• Bone marrow transplantation is a treatment option for those who do not respond well to drug treatments