Publication details

Analysis of chronic myeloid leukaemia during deep molecular response by genomic PCR: a traffic light stratification model with impact on treatment-free remission

Authors

MACHOVA POLAKOVA Katerina ZIZKOVA Hana ZUNA Jan MOTLOVA Eliska HOVORKOVA Lenka GOTTSCHALK Andrea GLAUCHE Ingmar KOBLIHOVA Jitka PECHERKOVA Pavla KLAMOVA Hana STASTNA MARKOVA Marketa SRBOVA Dana BENESOVA Adela POLIVKOVA Vaclava JURČEK Tomáš ŽÁČKOVÁ Daniela MAYER Jiří ERNST Thomas MAHON Francois X. SAUSSELE Susanne ROEDERVIEW Ingo CROSS Nicholas C. P. HOCHHAUS Andreas

Year of publication 2020
Type Article in Periodical
Magazine / Source Leukemia
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.nature.com/articles/s41375-020-0882-1#author-information
Doi http://dx.doi.org/10.1038/s41375-020-0882-1
Keywords chronic myeloid leukaemia; genomic PCR
Description 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.
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