Tests
1st tests to order
CBC and differential
Test
Should be ordered in patients with fatigue, fever, or bleeding disorders, with or without a history of chronic myeloid leukemia.
Result
elevated WBC count (>100 × 10⁹/L [100,000/microliter]), but may be normal or low; hemoglobin <7 g/dL; thrombocytopenia (platelets <100 × 10⁹/L [<100,000/microliter]); presence of blast cells
Tests to consider
peripheral blood smear
Test
Should be ordered in follow-up to CBC with differential for confirmation of diagnosis.
Diagnosis is confirmed by the percentage of blast cells in the peripheral blood and/or bone marrow (i.e., ≥20% [World Health Organization criteria, International Consensus Classification of Myeloid Neoplasms and Acute Leukemias]; or, ≥30% [MD Anderson Cancer Center, International Bone Marrow Transplant Registry criteria, and European LeukemiaNet criteria]), or the presence of an extramedullary proliferation of blasts.[1][2][26][27][28]
Subsequent to the introduction of tyrosine kinase inhibitor therapy, many clinical trials employ MD Anderson Cancer Center or International Bone Marrow Transplant Registry criteria.[2] MDACC criteria and International Bone Marrow Transplant Registry criteria are favored in clinical practice. See Criteria.
Result
blast cells ≥20% or ≥30% (depending on criteria)
bone marrow aspiration and biopsy for cytogenetic analysis
Test
Required for cytogenetic analysis (karyotyping) to establish the presence of Philadelphia chromosome, and to confirm the phase (proportion of blast cells and basophils) of CML.[29]
Diagnosis is confirmed by the percentage of blast cells in the peripheral blood and/or bone marrow (i.e., ≥20% [World Health Organization criteria, International Consensus Classification of Myeloid Neoplasms and Acute Leukemias]; or, ≥30% [MD Anderson Cancer Center, International Bone Marrow Transplant Registry criteria, and European LeukemiaNet criteria]), or the presence of an extramedullary proliferation of blasts.[1][2][26][27][28]
Subsequent to the introduction of tyrosine kinase inhibitor (TKI) therapy, many clinical trials employ MD Anderson Cancer Center or International Bone Marrow Transplant Registry criteria.[2] MDACC criteria and International Bone Marrow Transplant Registry criteria are favored in clinical practice. See Criteria.
Bone marrow cytogenetics can detect additional chromosomal abnormalities (ACAs; also known as clonal cytogenetic evolution) in Ph-positive and Ph-negative cells.[29] ACAs may be associated with TKI resistance and poor prognosis.[2]
Result
positive for Philadelphia chromosome; blast cells ≥20% or ≥30% (depending on criteria); additional chromosomal abnormalities in Ph-positive (trisomy 8, isochromosome 17q, second Ph, trisomy 19, and chromosome 3 abnormalities) or Ph-negative cells (trisomy 8 and loss of the Y chromosome)
quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR)
Test
CML can be confirmed by detection of BCR::ABL1 abnormalities on molecular analysis (qRT-PCR).[2][29][32]
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).[30] 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.[2][29]
Result
variable levels of BCR::ABL1 mRNA transcript
fluorescence in situ hybridization
Test
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.
Result
positive for BCR::ABL1 rearrangement
flow cytometry
Test
May be carried out on bone marrow biopsy (or alternatively peripheral blood) to determine blast cell lineage (e.g., myeloid, lymphoid, or mixed lineage).[2][32]
Can identify distinct populations of blast cells (e.g., CD34 positive).
Result
identifies blast cells of myeloid, lymphoid, or mixed lineage
mutational analysis
Test
Performed to identify mutations associated with tyrosine kinase inhibitor (TKI) resistance.
BCR::ABL1 kinase domain mutation analysis (next generation sequencing, if available) should be carried out for patients who have progressed to blast crisis while receiving TKI therapy, or who have an inadequate response to TKI therapy.[2][29]
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.[2][29][32]
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
HLA1 testing
lumbar puncture
serum leukocyte alkaline phosphatase
Test
Not required for diagnosis of blast crisis.
May also be seen in other phases of chronic myeloid leukemia.
Result
low
serum vitamin B12
Test
Not required for diagnosis of blast crisis.
May also be seen in other phases of chronic myeloid leukemia.
Result
high
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