A 58-year-old man from Delhi presents with a 6-month history of fatigue and abdominal discomfort. On examination, he has splenomegaly. CBC shows WBC 85,000/µL with 60% neutrophils, 15% metamyelocytes, 10% myelocytes, and 5% blasts. Bone marrow aspirate confirms chronic myeloid leukemia (CML) in chronic phase. Cytogenetics shows t(9;22). What is the most appropriate next step in management?

Explanation

## Diagnosis and Baseline Assessment **Key Point:** CML diagnosis is confirmed by t(9;22) cytogenetics and/or BCR-ABL fusion. Before initiating tyrosine kinase inhibitor (TKI) therapy, baseline BCR-ABL transcript quantification is mandatory for monitoring response and detecting resistance mutations. ## Management Algorithm for CML in Chronic Phase ```mermaid flowchart TD A[CML Chronic Phase Confirmed]:::outcome --> B[Baseline BCR-ABL qPCR]:::action B --> C[Assess Sokal/Hasford Score]:::action C --> D[Start TKI: Imatinib 1st line]:::action D --> E[Monitor qPCR at 3, 6, 12 months]:::action E --> F{BCR-ABL transcript level?}:::decision F -->|< 10% IS at 3 mo| G[Continue imatinib]:::action F -->|≥ 10% IS at 3 mo| H[Check mutation, switch to 2nd-gen TKI]:::urgent F -->|Complete cytogenetic response| I[Maintain therapy, long-term follow-up]:::outcome ``` ## Why Baseline qPCR is Essential | Aspect | Significance | |--------|-------------| | **Baseline transcript level** | Predicts TKI response and prognosis | | **Monitoring timepoints** | 3, 6, 12 months, then annually | | **Milestone criteria** | BCR-ABL ≤10% IS at 3 months = optimal response | | **Resistance detection** | Identifies kinase domain mutations early | **High-Yield:** Imatinib mesylate is the first-line TKI for CML chronic phase, with a dose of 400 mg daily. Baseline qPCR establishes the starting point for assessing molecular response. **Clinical Pearl:** The International Scale (IS) standardizes BCR-ABL reporting across laboratories, enabling comparison of results over time and between institutions. ## Why Other Options Are Incorrect - **Hydroxyurea alone:** Cytoreductive but does not target BCR-ABL; no longer standard of care for CML. - **Direct SCT without TKI trial:** Allogeneic transplant is reserved for TKI-resistant disease or advanced phases; chronic phase patients should receive TKI first. - **Interferon-alpha:** Historical therapy, now obsolete; inferior to TKI and associated with significant toxicity. [cite:Harrison 21e Ch 104]