Chronic Myeloid Leukemia

Chronic myeloid leukaemia (CML) is a myeloproliferative neoplasm driven by BCR::ABL1 (Philadelphia chromosome, t(9;22)).

• Incidence 1 to 2 per 100,000; median age 55 to 65.
• Phases: chronic (about 90% at diagnosis), accelerated, blast crisis (myeloid 70%, lymphoid 30%).
• Constitutive tyrosine kinase activity drives proliferation.
• With TKI therapy, life expectancy approaches normal.

• Fatigue, weight loss, night sweats, early satiety, left upper quadrant discomfort from splenomegaly, gout.
• Often incidental leucocytosis.
• Rare priapism, visual disturbance, thrombosis (leukostasis).
• Accelerated/blast phase: fever, bone pain, bleeding, infection.

• Leucocytosis (often over 100 x 10^9/L) with left shift, basophilia and eosinophilia, thrombocytosis, low leucocyte alkaline phosphatase.
• BCR::ABL1 by FISH and quantitative RT-PCR (International Scale, IS), marrow cytogenetics (Ph, additional chromosomal abnormalities).
• Phase definition: blasts 15% or more (accelerated, 10 to 19% ELN) and 20% or more (blast crisis); basophils over 20%.
• Risk scores (Sokal, ELTS), uric acid, LDH, ECG for QTc and cardiovascular baseline, hepatitis B screen.

• First line TKI: imatinib 400 mg daily, dasatinib 100 mg daily, nilotinib 300 mg twice daily, bosutinib 400 mg daily, or asciminib 80 mg daily; choose by risk, comorbidities (nilotinib avoided with cardiovascular disease and diabetes; dasatinib with pulmonary disease; bosutinib with GI problems).
• Monitoring: BCR::ABL1 IS every 3 months: optimal responses are 10% or less at 3 months, 1% or less at 6 months, 0.1% (MMR) or less at 12 months.
• Failure or intolerance: switch TKI after mutation analysis (T315I: ponatinib 45 mg daily, asciminib 200 mg twice daily, olverembatinib); allogeneic transplant for resistant disease or blast crisis.
• Treatment free remission attempt after at least 3 to 5 years of TKI with sustained deep molecular response (MR4 or better for 2 years); relapse in about 50% (most within 6 months), requiring monthly monitoring initially.
• Hydroxyurea 1 to 4 g daily or leucapheresis for leucostasis before TKI.
• Pregnancy: stop TKI (teratogenic); interferon alpha if needed.
• Adverse effects: imatinib (oedema, cramps), dasatinib (pleural effusion), nilotinib (QTc, atherosclerosis), ponatinib (arterial occlusion). Manage cardiovascular risk.
• Blast crisis: TKI with induction chemotherapy (AML or ALL regimen) then transplant.