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Molecular response (MMR, MR4, treatment-free remission)

aka major molecular response, MR4, MR4.5, deep molecular response, complete molecular response, BCR-ABL1 transcript, BCR::ABL1 IS, International Scale, treatment-free remission, TFR, molecular relapse, cytogenetic response, complete cytogenetic response, early molecular response

In chronic myeloid leukaemia, how far the leukaemia gene signal in the blood has fallen, measured in logs: a 1,000-fold drop is a major molecular response, a 10,000-fold drop (MR4) is 'deep'. Deep responses held for two years let some patients stop their pills.

Quantitative PCR for BCR::ABL1 transcripts on the International Scale defines milestones: ≤10% at 3 months (early molecular response), ≤1% (complete cytogenetic response equivalent), ≤0.1% (MMR) by 12 months, ≤0.01% (MR4) and ≤0.0032% (MR4.5). Missing milestones triggers a switch of TKI. Sustained deep response for at least two years permits a supervised stop; about half stay in treatment-free remission and the rest regain response on restarting (EURO-SKI). 'Molecular relapse' is a rising transcript before any clinical sign. The concept is being borrowed for ctDNA-guided stopping in solid tumours.

Category
Pathology & biomarkers

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