Analysis of chronic myeloid leukaemia during deep molecular response by genomic PCR: a traffic light stratification model with impact on treatment-free remission
| Authors | |
|---|---|
| Year of publication | 2020 |
| Type | Article in Periodical |
| Magazine / Source | Leukemia |
| MU Faculty or unit | |
| 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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