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Review
. 2021 Jul 22;11(8):697.
doi: 10.3390/jpm11080697.

Treatment-Free Remission-A New Aim in the Treatment of Chronic Myeloid Leukemia

Paulina Kwaśnik  1 , Krzysztof Giannopoulos  1   2
Affiliations
Review

Treatment-Free Remission-A New Aim in the Treatment of Chronic Myeloid Leukemia

Paulina Kwaśnik et al. J Pers Med. .

Abstract

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.

Keywords: TKI withdrawal syndrome; chronic myeloid leukemia (CML); treatment-free remission (TFR); tyrosine kinases inhibitors (TKIs).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Steps to follow to achieve TFR from diagnosis of CML, detection of individual mutations, treatment of TKI to stable deep molecular remission (DMR), and then discontinuation of treatment (TFR) with 50% success or molecular relapse, prompting re-initiation of treatment to re-attain DMR and eventually make a second attempt to discontinuation treatment (2nd TFR). A scheme to include younger patients with low- to medium-risk disease and women who wish to become pregnant for whom TFR has a high priority.
See this image and copyright information in PMC

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