Tests
1st tests to order
CBC
Test
The vast majority of patients with CML have an elevated WBC count, and half have a WBC count >100,000/microliter.[31] Anemia and thrombocytosis may be present.[31][32]
Persistent or increasing WBC (unresponsive to treatment), persistent thrombocytosis (unresponsive to treatment), or persistent thrombocytopenia (unrelated to therapy) would categorize the patient in accelerated phase based on the WHO criteria.[36]
CBC is used for subsequent disease monitoring. Complete hematologic response to therapy is measured by normalization of CBC parameters.
Result
elevated WBC count; anemia; normal platelet count, thrombocytosis (chronic or accelerated phases), or thrombocytopenia (accelerated or blast crisis)
complete metabolic profile
Test
There may be no specific abnormality, or potassium, LDH, and uric acid may be elevated due to extensive cell turnover.
Result
may have elevated potassium, LDH, or uric acid; pseudohyperkalemia may be present, necessitating whole blood or plasma potassium investigation
peripheral blood smear
Test
Almost all WBCs are mature or maturing myeloid cells (left shift of myeloid elements is typical).
Can be used for subsequent disease monitoring.
Absolute basophil count ≥20% would categorize the patient in accelerated phase based on the WHO criteria.[36]
Result
mature or maturing myeloid cells, including band forms, metamyelocytes, myelocytes, promyelocytes, and limited blast forms; elevated basophils and eosinophils
bone marrow aspirate and biopsy for cytogenetic analysis
Test
CML can be confirmed by the presence of the Philadelphia (Ph) chromosome, t(9;22)(q34;q11), on bone marrow evaluation.[5][34][37]
All patients should have a bone marrow evaluation to establish the diagnosis and phase of CML.[5]
In addition to the Ph chromosome, bone marrow cytogenetic analysis can detect additional chromosomal abnormalities (ACAs) in Ph-positive and Ph-negative cells, which may have negative prognostic impact. Analysis of 20-25 metaphase cells is recommended.[5][34]
Result
granulocytic hyperplasia; blast percentage (to properly ascertain the presence of accelerated or blast phase of disease); positive for Philadelphia chromosome; ACAs in Ph+ cells (trisomy 8, isochromosome 17q, second Ph, trisomy 19, and chromosome 3 abnormalities) or in Ph- cells (trisomy 8 and loss of the Y chromosome)
quantitative reverse transcription PCR (qRT-PCR) including breakpoint analysis
Test
CML can be confirmed by detection of BCR::ABL1 abnormalities on molecular analysis (qRT-PCR).[5][34][37]
Molecular analysis using qRT-PCR on peripheral blood should be carried out at initial workup to establish the presence of quantifiable BCR::ABL1 mRNA transcripts.
Laboratories should report qRT-PCR results according to an international scale (IS).[35]
qRT-PCR is highly sensitive and it is the only quantitative method of assessing molecular response to therapy; regular qRT-PCR monitoring is recommended following diagnosis (every 3 months).[5][34]
Around 1/10⁵ to 1/10⁶ leukemic cells can be detected with this method.[1]
Result
BCR::ABL1 mRNA transcripts
fluorescence in situ hybridization (FISH)
Test
CML can be confirmed by detection of BCR::ABL1 abnormalities on FISH analysis.[5][34][37]
FISH can be performed on bone marrow aspirate or peripheral blood to identify BCR::ABL1 rearrangements. Used if bone marrow cytogenetic evaluation is not possible or if results of cytogenetics and qRT-PCR differ. It is sometimes used as an initial screening test or, if qRT-PCR is not available, for disease monitoring. FISH cannot detect ACAs.[5][34]
FISH is not recommended for monitoring response if conventional cytogenetics or qRT-PCR are available.
Result
BCR::ABL1 rearrangement, t(9;22)
Tests to consider
mutational analysis
Test
Performed to identify mutations associated with tyrosine kinase inhibitor (TKI) resistance.
BCR::ABL1 kinase domain mutation analysis (using next-generation sequencing) should be carried out for patients with chronic-phase disease who have an inadequate response to TKI therapy, and those diagnosed with or who progress to advanced disease.[5]
Next-generation sequencing with a myeloid mutation panel may be considered in patients with no identified BCR::ABL1 kinase domain mutations to detect low-level BCR::ABL1 kinase domain mutations or BCR::ABL1-independent resistance mutations.[5][34]
Result
BCR::ABL1 kinase domain mutation analysis may be positive for mutations associated with TKI resistance (e.g., T315I gene mutation associated with resistance to imatinib, bosutinib, dasatinib, nilotinib); myeloid mutation panel may identify mutations in epigenetic modifier genes (e.g., ASXL1) that are associated with lower response rates and reduced progression-free survival
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