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Vol 53, No 3 (2022)
Review article
Submitted: 2022-02-03
Accepted: 2022-02-11
Published online: 2022-04-05
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Chronic myeloid leukemia: where do we stand, where can we go?

Krzysztof Lewandowski1, Jakub Lewandowski2
DOI: 10.5603/AHP.a2022.0012
·
Acta Haematol Pol 2022;53(3):153-165.
Affiliations
  1. Department of Hematology and Bone Marrow Transplantation, Poznań University of Medical Sciences, Poznań, Poland
  2. Faculty of Chemistry, Adam Mickiewicz University, Poznań, Poland

open access

Vol 53, No 3 (2022)
REVIEW ARTICLE
Submitted: 2022-02-03
Accepted: 2022-02-11
Published online: 2022-04-05

Abstract

The introduction of BCR-ABL tyrosine kinase inhibitors to the treatment of chronic myeloid leukemia (CML) has significantly changed the long term therapy results.

After an initial 12 months of therapy with tyrosine kinase inhibitor (TKI), a 3-log reduction of the BCR-ABL copies number on an international scale is possible in 22–46% of patients, depending on the TKI used. In TKI-responsive patients, long-term TKI treatment results are even better, with the BCR-ABL transcript level decreasing over time, even to the point of becoming undetectable. Therefore, an operational cure can be diagnosed in CML patients with an optimal response to 1st-line TKI treatment, atherapy duration of longer than 5–8 years, and BCR-ABL transcript level below MR4.0–MR4.5 for a period of more than two years. The latter has been the basis of multiple concepts of permanent or periodic discontinuation of TKI treatment [treatment-free remission (TFR)]. Initial TKI discontinuation clinical trials resulted in satisfactory results, with a disease recurrence rate of c.40–60% after 2–3 years. The mechanism of disease recurrence was then studied , with detailed characterization of the CML stem cells (CML SCs) immunophenotype and the mechanisms of survival and self-renewal under TKI selective pressure. A better understanding of the biology of CML allowed the formulation of new therapy concepts of CML SCs eradication, and new criteria for successful TFR qualification.

Abstract

The introduction of BCR-ABL tyrosine kinase inhibitors to the treatment of chronic myeloid leukemia (CML) has significantly changed the long term therapy results.

After an initial 12 months of therapy with tyrosine kinase inhibitor (TKI), a 3-log reduction of the BCR-ABL copies number on an international scale is possible in 22–46% of patients, depending on the TKI used. In TKI-responsive patients, long-term TKI treatment results are even better, with the BCR-ABL transcript level decreasing over time, even to the point of becoming undetectable. Therefore, an operational cure can be diagnosed in CML patients with an optimal response to 1st-line TKI treatment, atherapy duration of longer than 5–8 years, and BCR-ABL transcript level below MR4.0–MR4.5 for a period of more than two years. The latter has been the basis of multiple concepts of permanent or periodic discontinuation of TKI treatment [treatment-free remission (TFR)]. Initial TKI discontinuation clinical trials resulted in satisfactory results, with a disease recurrence rate of c.40–60% after 2–3 years. The mechanism of disease recurrence was then studied , with detailed characterization of the CML stem cells (CML SCs) immunophenotype and the mechanisms of survival and self-renewal under TKI selective pressure. A better understanding of the biology of CML allowed the formulation of new therapy concepts of CML SCs eradication, and new criteria for successful TFR qualification.

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Keywords

chronic myeloid leukemia, tyrosine kinase inhibitors, chronic myeloid leukemia stem cells, immune system escape, treatment-free remission, new treatment concepts

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About this article
Title

Chronic myeloid leukemia: where do we stand, where can we go?

Journal

Acta Haematologica Polonica

Issue

Vol 53, No 3 (2022)

Article type

Review article

Pages

153-165

Published online

2022-04-05

Page views

3015

Article views/downloads

256

DOI

10.5603/AHP.a2022.0012

Bibliographic record

Acta Haematol Pol 2022;53(3):153-165.

Keywords

chronic myeloid leukemia
tyrosine kinase inhibitors
chronic myeloid leukemia stem cells
immune system escape
treatment-free remission
new treatment concepts

Authors

Krzysztof Lewandowski
Jakub Lewandowski

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