This work investigated patient-specific genomic BCR-ABL1 fusions as markers of measurable residual disease (MRD) in chronic myeloid leukaemia, with a focus on relevance to treatment-free remission (TFR) after achievement of deep molecular response (DMR) on tyrosine kinase inhibitor (TKI) therapy. DNA and mRNA BCR-ABL1 measurements by qPCR were compared in 2189 samples (129 patients) and by digital PCR in 1279 sample (62 patients). A high correlation was found at levels of disease above MR4, but there was a poor correlation for samples during DMR. A combination of DNA and RNA MRD measurements resulted in a better prediction of molecular relapse-free survival (MRFS) after TKI stop (n = 17) or scheduled interruption (n = 25). At 18 months after treatment cessation, patients with stopped or interrupted TKI therapy who were DNA negative/RNA negative during DMR maintenance (green group) had an MRFS of 80% and 100%, respectively, compared with those who were DNA positive/RNA negative (MRFS = 57% and 67%, respectively; yellow group) or DNA positive/RNA positive (MRFS = 20% for both cohorts; red group). Thus, we propose a "traffic light" stratification as a TFR predictor based on DNA and mRNA BCR-ABL1 measurements during DMR maintenance before TKI cessation.

Abteilung Hämatologie Onkologie Klinik für Innere Medizin 2 University of Jena Jena Germany

BERGONIE Institute BORDEAUX INSERM U1218 University of Bordeaux Bordeaux France

Center of Molecular Biology and Gene Therapy Internal Hematology and Oncology Clinic Faculty Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

CLIP Department of Paediatric Haematology and Oncology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Department of Haematology and Oncology University Hospital Mannheim Heidelberg University Mannheim Germany

Institute for Medical Informatics and Biometry Carl Gustav Carus Faculty of Medicine TU Dresden Dresden Germany

Institute of Clinical and Experimental Hematology 1st Faculty of Medicine Charles University Prague Czech Republic

Institute of Hematology and Blood Transfusion Prague Czech Republic

Institute of Pathological Physiology 1st Faculty of Medicine Charles University Prague Czech Republic

Internal Hematology and Oncology Clinic Faculty Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

National Center for Tumor Diseases Partner Site Dresden Dresden Germany

Wessex Regional Genetics Laboratory Salisbury NHS Foundation Trust Salisbury and Faculty of Medicine University of Southampton Southampton UK

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