This test guide provides an overview of tests that assist with the diagnosis, classification, prognosis, and management of chronic myeloid leukemia, formerly called chronic myelogenous leukemia (CML). It is provided for informational purposes only and is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the physician's education, clinical expertise, and assessment of the patient.

CML is a hematopoietic stem cell cancer characterized by uncontrolled expansion of myeloid cells.¹ In 90% to 95% of patients, CML is caused by a characteristic translocation¹ between chromosomes 9 and 22. This translocation results in an abnormally short chromosome 22—the Philadelphia chromosome (Ph)—and formation of the BCR-ABL1 fusion gene.¹ The fusion gene produces a constitutively active tyrosine kinase that causes CML.¹ The remaining 5% to 10% of patients have a translocation involving 3 or 4 chromosomes or a cryptic translocation that cannot be detected by karyotyping.¹

Diagnosis and prognosis

According to the latest World Health Organization guidance, CML has 2 phases of progression: the initial chronic phase and the blast phase.¹ When blood morphology findings suggest CML, the diagnosis is confirmed by identifying Ph using karyotyping and/or by detecting the BCR-ABL1 fusion gene with polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH) tests.^1,2 Once CML is diagnosed, determining disease phases (chronic or blast phase) can help assess prognosis and select therapy.^1,2 Patients in chronic phase with high-risk features are more likely to have disease progression and resistance to tyrosine kinase inhibitors (TKIs). Figure 1 shows criteria that can be used in laboratory diagnosis and determining the phases and high-risk features of CML.^1,2

Therapy selection and monitoring

CML treatments mainly include therapy with a TKI (eg, asciminib, bosutinib, dasatinib, nilotinib, or imatinib) and allogeneic hematopoietic stem cell transplantation.² Laboratory tests that assess hematologic (test code 6399), cytogenetic (test code 14600), and molecular (test code 91065) disease levels can be used to monitor response to TKI therapy (Table 1 and Figure 2).^2-4 The FISH test (test code 12070) is not recommended to routinely monitor response to TKI therapy^2,3 but is useful for monitoring rare or atypical transcripts.⁴ Although these therapies induce durable responses in most patients with chronic-phase CML, some patients fail to respond (primary resistance) or lose their response (secondary resistance) to therapy.⁵ The most common cause of resistance is mutation in the ABL1 kinase domain.⁵ Laboratory tests that evaluate ABL1 kinase domain mutations may help guide treatment change when patients develop primary or secondary resistance to TKI therapy (Figure 3).^2,4,6,7 ABL1 kinase domain mutation analysis is also recommended to help select initial treatment for patients with blast-phase CML (Figure 3).² 

Table 1. Classification of Treatment Response

IS, international scale; MR, molecular response; PB, peripheral blood; PCR, polymerase chain reaction; Ph+, positive for the Philadelphia chromosome; WBC, white blood cell.
a	Out of ≥20 metaphase cells.
b	Corresponds to a ≥3-log decrease in BCR-ABL1 transcript levels from standardized baseline.

 

Figure 2. Use of Laboratory Tests to Monitor Response to TKI Therapy in CML Patients

Figure 3. Uses of ABL Kinase Domain Mutation Analysis to help select TKI therapy

 

Table 2 provides an overview of the types of laboratory tests used for diagnosing CML with recognizing CML phases, determining prognosis, and monitoring treatment response.

Table 2. Laboratory Tests Useful for CML Diagnosis, Classification, Prognosis, and Monitoring of TKI Treatment Response

Test code	Test name	Clinical use
Hematology, morphology, and comprehensive tests
6399	CBC (Includes Differential and Platelets)	Diagnose and classify CML, assess prognosis and monitor treatment response
17734(X)a	Comprehensive Hematopathology Report Includes morphology evaluation; may include chromosome analysis, BCR-ABL1 PCR test, BCR-ABL1 FISH test, and/or ABL1 kinase domain mutation analysis.
Cytogenetic and FISH tests
14600	Chromosome Analysis, Hematologic Malignancy	Diagnose and classify CML, assess prognosis and monitor treatment response
12070b	FISH, CML/ALL, bcr/abl, Translocation 9,22	Diagnose CML (alternative to karyotyping), monitor rare or atypical transcripts
Molecular tests
91065b	BCR-ABL1 Gene Rearrangement, Quantitative PCR	Diagnose and classify CML, assess prognosis and monitor treatment response
16029b	ABL Kinase Domain Mutation	Select treatment for blast-phase CML and primary or secondary TKI resistance (predicts resistance to asciminib, bosutinib, dasatinib, imatinib, or nilotinib)c

AMP/ASCO/CAP, Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists; BM, bone marrow; CBC, complete blood count; CML, chronic myeloid leukemia; FISH, fluorescence in situ hybridization; PCR, polymerase chain reaction; TKI, tyrosine kinase inhibitor.
a	Test results are reviewed by a hematopathologist, and if deemed medically necessary for evaluation, additional tests are performed at an additional charge. CPT codes vary depending on the specific tests ordered. Test code 17734 includes an interpretive report issued by a hematopathologist.
b	This test was developed and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
c	Rare or emerging mutations associated with TKI resistance6 or variants of unknown clinical significance will also be reported per AMP/ASCO/CAP.7