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?

Question

Accepted Answer

A. Perform BCR-ABL quantitative PCR (qPCR) and start imatinib mesylate. ## 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]

![Chronic Leukemias diagram](https://mmcphlazjonnzmdysowq.supabase.co/storage/v1/object/public/blog-images/explanation/2642.webp)

Answer

B. Start interferon-alpha and monitor with bone marrow biopsy every month

Answer

C. Start hydroxyurea immediately and repeat CBC in 2 weeks

Answer

D. Refer for allogeneic stem cell transplantation without further testing

Explanation

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Diagnosis and Baseline Assessment

Management Algorithm for CML in Chronic Phase

Why Baseline qPCR is Essential

Why Other Options Are Incorrect

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