Diagnosis and Management of Chronic Myeloid Leukemia (CML)

Essential Diagnostic Criteria

The European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) recommend that the diagnosis of CML requires demonstration of the Philadelphia chromosome (Ph) or BCR-ABL1 fusion gene in a patient with characteristic peripheral blood findings showing excessive granulocytosis with left shift 1, 2
A complete blood count with differential typically shows excessive granulocytosis with a left shift of granulopoiesis, including immature granulocytes such as myelocytes and metamyelocytes 1
The white blood cell count often exceeds 100 × 10⁹/L at presentation, with basophilia and eosinophilia also common 3

The American Society of Clinical Oncology (ASCO) and ESMO recommend bone marrow cytogenetics to detect the t(9;22)(q34;q11) translocation and identify any additional chromosomal abnormalities 4, 3
Qualitative RT-PCR on blood or bone marrow is used to identify the BCR-ABL1 transcript type, typically e13a2 or e14a2 5
Quantitative RT-PCR is used to establish baseline BCR-ABL1 transcript levels on the International Scale (IS) 4, 5

The European LeukemiaNet (ELN) criteria define chronic phase as <15% blasts in blood and bone marrow, which is the presentation phase for 90-95% of patients 1, 3
Accelerated phase is defined by 15-29% blasts in peripheral blood or bone marrow, according to ELN criteria 1, 3
Blast phase is defined by ≥30% blasts in peripheral blood or bone marrow or extramedullary blast involvement, according to ELN criteria 1, 3

ESMO and NCCN guidelines recommend a complete baseline diagnostic workup, including history and physical examination, laboratory studies, bone marrow studies, and molecular studies 4, 3, 5
The initial evaluation must include palpation of the spleen, hepatomegaly, and constitutional symptoms, as well as complete blood count with differential, chemistry profile, and hepatitis B panel 3, 4
Bone marrow studies should include aspirate for morphology and cytology, biopsy for histology and assessment of fibrosis, and cytogenetics to detect additional chromosomal abnormalities 5, 4
Molecular studies should include qualitative RT-PCR to identify transcript type and quantitative RT-PCR to establish baseline BCR-ABL1 levels 5, 4