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 journalResearch articleContributedpeer-review

Contributors

  • Katerina Machova Polakova - , Institute of Hematology and Blood Transfusion (Author)
  • Hana Zizkova - , Institute of Hematology and Blood Transfusion (Author)
  • Jan Zuna - , University Hospital Motol (Author)
  • Eliska Motlova - , Institute of Hematology and Blood Transfusion (Author)
  • Lenka Hovorkova - , University Hospital Motol (Author)
  • Andrea Gottschalk - , Institute for Medical Informatics and Biometry (Author)
  • Ingmar Glauche - , Institute for Medical Informatics and Biometry (Author)
  • Jitka Koblihova - , Institute of Hematology and Blood Transfusion (Author)
  • Pavla Pecherkova - , Institute of Hematology and Blood Transfusion (Author)
  • Hana Klamova - , Institute of Hematology and Blood Transfusion (Author)
  • Marketa Stastna Markova - , Institute of Hematology and Blood Transfusion (Author)
  • Dana Srbova - , Institute of Hematology and Blood Transfusion (Author)
  • Adela Benesova - , Institute of Hematology and Blood Transfusion (Author)
  • Vaclava Polivkova - , Institute of Hematology and Blood Transfusion (Author)
  • Tomas Jurcek - , Masaryk University (Author)
  • Daniela Zackova - , Masaryk University (Author)
  • Jiri Mayer - , Masaryk University (Author)
  • Thomas Ernst - , Jena University Hospital (Author)
  • Francois X Mahon - , Centre Georges-François Leclerc (Author)
  • Susanne Saussele - , Heidelberg University  (Author)
  • Ingo Roeder - , Institute for Medical Informatics and Biometry, National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Nicholas C P Cross - , University of Southampton (Author)
  • Andreas Hochhaus - , Jena University Hospital (Author)

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 languageEnglish
Pages (from-to)2113-2124
Number of pages12
JournalLeukemia
Volume34
Issue number8
Publication statusPublished - Aug 2020
Peer-reviewedYes

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

Library keywords