A 65-year-old man presents with splenomegaly, leucocytosis (WBC 120×10⁹/L) with a myeloid spectrum on smear, basophilia, and low leucocyte alkaline phosphatase (LAP) score. BCR-ABL1 translocation is confirmed. He is started on imatinib. What is the target of molecular response that defines 'deep molecular response' (MR4.5) used to consider treatment-free remission eligibility?

• A Complete haematological response with normal blood count
• B BCR-ABL1 transcript ratio less than 0.0032% on international scale ✓
• C Cytogenetic complete response (0% Philadelphia-positive metaphases)
• D BCR-ABL1 ratio below 10% at 3 months

Explanation

In CML, molecular responses are defined on the international scale (IS): major molecular response (MMR/MR3) is BCR-ABL1 IS ≤0.1%, MR4 is ≤0.01%, and MR4.5 (deep molecular response) is ≤0.0032%. Treatment-free remission (TFR) trials (ENESTfreedom, EURO-SKI) require sustained MR4 or MR4.5 for at least 2 years on TKI therapy before attempting TFR. Complete haematological and cytogenetic responses are earlier milestones, not criteria for TFR eligibility.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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