Key Questions for Screening Chronic Myeloid Leukemia (CML)
When screening for CML, diagnostic testing should include bone marrow cytogenetics, measurement of BCR-ABL transcript numbers by QPCR, and peripheral blood FISH analysis using dual probes for BCR and ABL genes. 1
Initial Screening Questions
Medical History
- Questions about fatigue, unexplained weight loss, night sweats
- History of bleeding tendencies (petechiae, bruising, prolonged bleeding)
- Presence of abdominal discomfort or early satiety (suggesting splenomegaly)
- Bone pain or joint pain
- Fever or recurrent infections
- History of prior radiation exposure
Physical Examination Focus
- Spleen size assessment (splenomegaly is common in CML)
- Presence of lymphadenopathy
- Skin examination for petechiae or bruising
- Liver size assessment (hepatomegaly may be present)
Laboratory Testing Algorithm
First-Line Diagnostic Tests
Complete Blood Count (CBC) with manual differential 1
- Look for leukocytosis (elevated WBC count)
- Presence of immature granulocytes in peripheral blood
- Platelet count (may be elevated or decreased)
- Basophilia (>20% suggests advanced disease)
Peripheral Blood FISH Analysis 1
- Using dual probes for BCR and ABL genes
- Acceptable as initial screening method when bone marrow collection is not feasible
Bone Marrow Examination 1
- Cytogenetics to detect Philadelphia chromosome
- Assessment of blast percentage (<10% in chronic phase)
Molecular Testing 1
- Qualitative RT-PCR to determine BCR-ABL transcript type
- Quantitative RT-qPCR to measure BCR-ABL transcript numbers
Differential Diagnosis Questions
- Questions to rule out other causes of leukocytosis (infections, inflammatory conditions)
- History of other myeloproliferative disorders
- Family history of leukemia or hematologic disorders
- Medication history that might affect blood counts
Risk Assessment Questions
- Age (CML incidence increases with age)
- Prior exposure to radiation or chemotherapy
- History of other cancers
- Comorbidities that might affect treatment options
Pitfalls to Avoid
- Don't rely solely on CBC: While leukocytosis is common in CML, confirmation requires cytogenetic or molecular testing for the Philadelphia chromosome or BCR-ABL fusion gene 1
- Don't miss variant translocations: About 5% of CML patients have a normal karyotype by conventional cytogenetics but still have BCR-ABL fusion 1
- Don't confuse with other myeloproliferative neoplasms: Ensure proper differentiation from conditions like chronic neutrophilic leukemia or atypical CML 2
Special Considerations
- For patients with suspected leukemia-predisposing conditions, more frequent monitoring may be required 1
- In cases with eosinophilia, specifically exclude rearrangements of PDGFRA and PDGFRB 1
- Consider NGS panel testing for patients presenting with blast phase CML to identify additional mutations that may guide therapy 1
Remember that the definitive diagnosis of CML requires demonstration of the Philadelphia chromosome by cytogenetics or the BCR-ABL fusion gene by molecular testing, as these are the hallmarks of the disease 3, 4.