A 55-year-old woman with CML on imatinib for 3 years achieves complete hematologic and cytogenetic response but BCR-ABL transcript level by PCR is 0.15% IS (MR3.0, major molecular response). After 6 months, BCR-ABL rises to 2% IS confirmed on repeat testing. The most appropriate next step is:

• A Continue imatinib and recheck in 3 months
• B Proceed to allogeneic SCT immediately
• C Add hydroxyurea to imatinib
• D Mutation analysis of BCR-ABL kinase domain and switch to second-generation TKI ✓

Explanation

Rising BCR-ABL transcript level (>1-log increase confirmed) constitutes molecular failure or suboptimal response to imatinib, with loss of MMR. Current ELN 2020 guidelines recommend BCR-ABL kinase domain mutation analysis (to detect T315I and other resistance mutations) followed by switch to a second-generation TKI (dasatinib, nilotinib, or bosutinib). T315I mutation requires ponatinib or asciminib. Continuing imatinib in the face of rising transcripts risks progression to blast crisis. Allogeneic SCT is reserved for blast phase or TKI-intolerant patients failing multiple TKIs.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.