Analysis of chronic myeloid leukaemia during deep molecular response by genomic PCR: a traffic light stratification model with impact on treatment-free remission
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
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.
Details
| Original language | English |
|---|---|
| Pages (from-to) | 2113-2124 |
| Number of pages | 12 |
| Journal | Leukemia |
| Volume | 34 |
| Issue number | 8 |
| Publication status | Published - Aug 2020 |
| Peer-reviewed | Yes |
External IDs
| Scopus | 85085695563 |
|---|---|
| ORCID | /0000-0002-2524-1199/work/142251500 |
| ORCID | /0000-0002-6741-0608/work/199962860 |
Keywords
Keywords
- Adult, Aged, Female, Fusion Proteins, bcr-abl/genetics, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy, Male, Middle Aged, Neoplasm, Residual, Polymerase Chain Reaction/methods, Protein Kinase Inhibitors/therapeutic use, Protein-Tyrosine Kinases/antagonists & inhibitors, RNA, Messenger/analysis, Remission Induction, Withholding Treatment