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Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia

Ilander, M.; Olsson-Strömberg, U.; Schlums, H.; Guilhot, J.; Brück, O.; Lähteenmäki, H.; Kasanen, T.; Koskenvesa, P.; Söderlund, S. and Höglund, M. LU , et al. (2017) In Leukemia 31(5). p.1108-1116
Abstract

Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug... (More)

Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naïve CD56bright NK cells had decreased relapse-free survival. In addition, the TNF-α/IFN-γ cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.

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Leukemia
volume
31
issue
5
pages
9 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85006312419
ISSN
0887-6924
DOI
10.1038/leu.2016.360
language
English
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yes
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b50be235-800d-40c2-a45e-e6f74fdec7b0
date added to LUP
2018-09-03 15:09:04
date last changed
2018-11-18 05:07:14
@article{b50be235-800d-40c2-a45e-e6f74fdec7b0,
  abstract     = {<p>Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naïve CD56<sup>bright</sup> NK cells had decreased relapse-free survival. In addition, the TNF-α/IFN-γ cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.</p>},
  author       = {Ilander, M. and Olsson-Strömberg, U. and Schlums, H. and Guilhot, J. and Brück, O. and Lähteenmäki, H. and Kasanen, T. and Koskenvesa, P. and Söderlund, S. and Höglund, M. and Markevärn, B. and Själander, A. and Lotfi, K. and Dreimane, A. and Lübking, A. and Holm, E. and Björeman, M. and Lehmann, S. and Stenke, L. and Ohm, L. and Gedde-Dahl, T. and Majeed, W. and Ehrencrona, H. and Koskela, S. and Saussele, S. and Mahon, F. X. and Porkka, K. and Hjorth-Hansen, H. and Bryceson, Y. T. and Richter, J. and Mustjoki, S.},
  issn         = {0887-6924},
  language     = {eng},
  month        = {05},
  number       = {5},
  pages        = {1108--1116},
  publisher    = {Nature Publishing Group},
  series       = {Leukemia},
  title        = {Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia},
  url          = {http://dx.doi.org/10.1038/leu.2016.360},
  volume       = {31},
  year         = {2017},
}