Journal
JOURNAL OF PERSONALIZED MEDICINE
Volume 11, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/jpm11080697
Keywords
chronic myeloid leukemia (CML); tyrosine kinases inhibitors (TKIs); treatment-free remission (TFR); TKI withdrawal syndrome
Funding
- National Science Center in Poland [NCN 2018/31/B/NZ6/03361]
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TKIs have revolutionized the treatment of chronic myeloid leukemia, achieving long-term remission without treatment in more than 40% of patients. The involvement of the immune system in preventing CML molecular relapse is emphasized, and modern technologies like ddPCR and NGS are essential for better identification of disease status in patients.
Tyrosine kinases inhibitors (TKIs) revolutionized chronic myeloid leukemia (CML) treatment for many years, prolonging patients' life expectancy to be comparable to age-matched healthy individuals. According to the latest the European LeukemiaNet (ELN) recommendations, CML treatment aims to achieve long-term remission without treatment (TFR), which is feasible in more than 40% of patients. Nearly all molecular relapses occur during the first 6 months after TKI withdrawal and do not progress to clinical relapse. The mechanisms that are responsible for CML relapses remain unexplained. It is suggested that maintaining TFR is not directly related to the total disposing of the gene transcript BCR-ABL1, but it might be a result of the restoration of the immune surveillance in CML. The importance of the involvement of immunocompetent cells in the period of TKI withdrawal is also emphasized by the presence of specific symptoms in some patients with withdrawal syndrome. The goal of this review is to analyze data from studies regarding TFRs in order to characterize the elements of the immune system of patients that might prevent CML molecular relapse. The role of modern droplet digital polymerase chain reaction (ddPCR) and next-generation sequencing (NGS) in better identification of low levels of BCR-ABL1 transcripts was also taken into consideration for refining the eligibility criteria to stop TKI therapy.
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