Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasm characterized by reciprocal translocation t(9;22)(q34;q11) creating the Philadelphia chromosome and BCR::ABL1 fusion oncogene that produces a constitutively active tyrosine kinase driving uncontrolled myeloid proliferation. Annual incidence is 1-2 per 100,000, with median age 64 years. CML progresses through three phases: chronic phase (>=85% of cases at diagnosis, indolent course with mature granulocyte expansion), accelerated phase (10-19% blasts, increased basophils, cytogenetic clonal evolution), and blast phase (>=20% blasts, behaves like acute leukemia, poor prognosis).
Diagnosis requires confirmation of BCR::ABL1 by reverse transcriptase PCR (quantitative for monitoring), fluorescence in situ hybridization (FISH), or cytogenetics showing t(9;22). Initial presentation is often incidental leukocytosis with left shift, mild anemia, thrombocytosis, and palpable splenomegaly. Symptoms when present include fatigue, weight loss, night sweats, abdominal fullness, and early satiety. Risk stratification uses Sokal, Hasford (Euro), or EUTOS-LTS scoring systems incorporating age, spleen size, blast percentage, basophils, eosinophils, and platelet count.
Tyrosine kinase inhibitors (TKIs) are the cornerstone of treatment, achieving complete cytogenetic response in >70% and deep molecular response (BCR::ABL1 IS <=0.01%) in 30-50% of patients. First-generation imatinib 400 mg daily is standard initial therapy with proven 10-year overall survival ~85%. Second-generation TKIs (dasatinib 100 mg daily, nilotinib 300 mg twice daily, bosutinib 400 mg daily) achieve faster and deeper molecular responses but with distinct toxicity profiles (dasatinib: pleural effusions, pulmonary hypertension; nilotinib: cardiovascular events, hyperglycemia; bosutinib: gastrointestinal toxicity). Third-generation ponatinib 45 mg daily targets T315I gatekeeper mutation but causes arterial thrombotic events. Asciminib (STAMP inhibitor) binds the myristoyl pocket allosterically, effective in resistance and approved for T315I and >=2 prior TKIs. Treatment-free remission can be attempted in patients with stable deep molecular response (MR4 or MR4.5) for >=2 years on TKI; approximately 50% achieve durable treatment-free remission with monitoring.