BCR-ABL1 transcript doubling time as a predictor for treatment-free remission failure after imatinib discontinuation in chronic myeloid leukaemia in chronic phase.
Adult
Aged
Biomarkers, Tumor
Child
Female
Fusion Proteins, bcr-abl
/ genetics
Gene Expression Regulation, Leukemic
Humans
Imatinib Mesylate
/ administration & dosage
Leukemia, Myeloid, Chronic-Phase
/ diagnosis
Male
Middle Aged
Protein Kinase Inhibitors
/ administration & dosage
Real-Time Polymerase Chain Reaction
Recurrence
Remission Induction
Treatment Failure
Young Adult
CML
IMATINIB
TKI discontinuation
doubling time
treatment-free remission
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
06
08
2021
received:
01
06
2021
accepted:
16
08
2021
pubmed:
9
9
2021
medline:
15
2
2022
entrez:
8
9
2021
Statut:
ppublish
Résumé
The doubling time (DT) of the BCR-ABL1 quantitative polymerase chain reaction (qPCR) transcript level reflects the re-growing fraction of leukaemic cells after discontinuation of tyrosine kinase inhibitor (TKI). The present study analyzed monthly DT within six months after imatinib discontinuation in 131 patients. Monthly DT was calculated as x = ln(2)/K, where x is the DT and K is the fold BCR-ABL1 change from the previous value divided by the number of days between each measurement. The optimal DT value was determined as 12·75 days at two months using a recursive partitioning method. The patients were stratified into three groups: the high-risk group (DT<12·75 days but >0, with rapidly proliferating chronic myeloid leukaemia (CML) cells; n = 26) showed the lowest molecular relapse-free survival (mRFS) of 7·7% at 12 months, compared to 53·6% in the intermediate-risk group (DT≥12·75 days, with slowly proliferating CML cells; n = 16) or 90·0% in the low-risk group (DT≤0, i.e., without proliferating CML cells; n = 71; P < 0·001). Monthly assessment of DT helps identify high-risk patients for treatment-free remission failure with an imminent risk of molecular recurrence, and to define low-risk patients who can be spared the frequent monitoring of monthly molecular tests.
Substances chimiques
BCR-ABL1 fusion protein, human
0
Biomarkers, Tumor
0
Protein Kinase Inhibitors
0
Imatinib Mesylate
8A1O1M485B
Fusion Proteins, bcr-abl
EC 2.7.10.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
136-145Informations de copyright
© 2021 British Society for Haematology and John Wiley & Sons Ltd.
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