Chronic Myeloid Leukemia

 

• Background

  Aka chronic myelogenous leukaemia.

  

  
  

  Pathophysiology

  • Clonal proliferation of myeloid stem cells which differentiate (unlike AML) into granulocytes.
  • 98% are due to chromosome 9-22 reciprocal translocation, creating the Philadelphia chromosome. ABL from Chr 9 fuses onto BCR on Chr 22 to create BCR-ABL fusion oncogene, encoding the p210 tyrosine kinase.
  • Chronic phase sometimes (5-10%) transforms into accelerated or blast phase, the latter leading to AML

  Epidemiology

  • Annual incidence: 1/100,000.
  • Peak age 40-60, slightly commoner in men.

• Signs and symptoms

  • Often asymptomatic.
  • Systemic: tired, malaise, weight loss, fever, night sweats.
  • Splenomegaly (75%), LUQ-discomfort/satiety (50%).
  • Cytopenia: pallor (anaemia), bleeding or bruising including epistaxis (thrombocytopaenia).
  • Gout/arthralgia (↑urate).

• Investigations

  FBC:

  • FBC: ↑↑WBC, can be >100.
  • Anaemia (50%).
  • ↑Platelets in chronic or accelerated phase, ↓platelets in blast phase.

  Blood film:

  • ↑Granulocytes especially neutrophils.

  Diagnosis:

  • Bone marrow biopsy: granulocytic hyperplasia.
  • Cytogenetics – blood or bone marrow – and FISH for Philadelphia Ch.
  • RT-PCR for BCR-ABL and disease monitoring.

• Management

  • Imatinib inhibits BCR-ABL p210 tyrosine kinase, and induces long-term remission. Side effects: cramps, oedema, rash, diarrhoea.
  • 2nd line: other TK inhibitors (TKI), such as nilotinib or dasatinib.
  • If no remission on TKI or relapse occurs, consider allogeneic stem cell transplant.
  • In blast phase, give both TKI and stem cell transplant.
  • Monitor with quantitative reverse transcription PCR (qRT-PCR) 3-monthly, and initially weekly FBC on treatment.

• Complications and prognosis

  • Worse prognosis if Philadelphia -ve.
  • 5 year survival: 90%, but complete BCR/ABL eradication rare (<5%).
  • 5 year disease free post-HSCT: 60% if sibling, 40% if unrelated.