Hematology Oncology · Year 2 · from Hematology Oncology
Case 1: Chronic Myeloid Leukemia (CML)
Patient Presentation
Demographics: 52-year-old male
Chief Complaint: Incidentally discovered elevated white blood cell count
History of Present Illness: The patient presented to his primary care physician for a routine health maintenance visit. He feels generally well but reports mild fatigue and early satiety over the past few months. He has noticed some left-sided abdominal fullness. He has no fever, night sweats, weight loss, or bone pain. Complete blood count obtained during the visit showed markedly elevated WBC.
Physical Examination:
- Vital signs: BP 132/82, HR 76, RR 14, Temp 36.8C
- General: Well-appearing middle-aged man
- HEENT: No lymphadenopathy
- Cardiac: Regular rhythm, no murmurs
- Lungs: Clear
- Abdomen: Splenomegaly extending 8 cm below left costal margin
- Skin: No petechiae, no bruising
- Neurologic: Normal
Workup and Results
Complete Blood Count:
- WBC: 125,000/uL
- Differential:
- Neutrophils: 45%
- Bands: 12%
- Metamyelocytes: 15%
- Myelocytes: 18%
- Promyelocytes: 4%
- Blasts: 2%
- Basophils: 6%
- Eosinophils: 4%
- Hemoglobin: 11.8 g/dL
- Platelets: 485,000/uL
Peripheral Blood Smear:
- Full spectrum of myeloid maturation ("myelocyte bulge")
- Basophilia and eosinophilia
- No significant dysplasia
- Occasional circulating blasts (<5%)
Additional Labs:
- LDH: 450 U/L (elevated)
- Uric acid: 8.5 mg/dL
- Leukocyte alkaline phosphatase (LAP) score: 8 (low; normal 30-150)
- Vitamin B12: 1,850 pg/mL (elevated)
Bone Marrow Biopsy:
- Hypercellular (95%)
- Marked myeloid hyperplasia
- 3% blasts (chronic phase)
- Cytogenetics: t(9;22)(q34;q11) - Philadelphia chromosome present
Molecular Testing:
- BCR-ABL1 by PCR: Positive (p210 transcript)
- BCR-ABL1 quantitative: 85% (International Scale)
Clinical Image
Peripheral blood smear in chronic myeloid leukemia demonstrating the full spectrum of myeloid maturation from blasts to mature neutrophils, with characteristic myelocyte bulge and basophilia.
Diagnosis
Chronic Myeloid Leukemia - Chronic Phase
Diagnostic criteria:
- Philadelphia chromosome positive t(9;22)
- BCR-ABL1 fusion gene present
- Chronic phase: <10% blasts, no accelerated/blast phase features
- Characteristic peripheral blood findings with low LAP score
Treatment Plan
- First-line tyrosine kinase inhibitor (TKI):
- Imatinib 400 mg daily, OR
- Second-generation TKI (dasatinib 100 mg daily or nilotinib 300 mg BID) for faster, deeper response
- Monitoring milestones:
- 3 months: BCR-ABL1 ≤10% (early molecular response)
- 6 months: BCR-ABL1 ≤1%
- 12 months: BCR-ABL1 ≤0.1% (major molecular response, MMR)
- Goal: Deep molecular response (MR4, MR4.5)
- Response assessment:
- Quantitative BCR-ABL1 PCR every 3 months
- Bone marrow at diagnosis and if suboptimal response
- Mutation analysis if treatment failure
- Long-term considerations:
- Near-normal life expectancy with TKI therapy
- Consider treatment-free remission (TFR) trial if sustained deep molecular response for ≥2 years
- Lifelong therapy if TFR not achieved
- If failure or intolerance:
- Switch to alternative TKI
- Mutation analysis (especially T315I which requires ponatinib)
- Consider allogeneic transplant for advanced disease
Teaching Points
- CML is defined by the Philadelphia chromosome creating BCR-ABL1 fusion tyrosine kinase
- The low LAP score distinguishes CML from leukemoid reaction (which has high LAP)
- TKI therapy has transformed CML from fatal disease to chronic manageable condition
- Monitoring BCR-ABL1 transcript levels is essential for assessing response
- Treatment-free remission is possible after sustained deep molecular response
- Disease phases: chronic (<10% blasts) → accelerated (10-19%) → blast crisis (≥20%)
- Basophilia is characteristic of CML and helps distinguish from other causes of leukocytosis