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Leukemia. 2017 May;31(5):1108-1116. doi: 10.1038/leu.2016.360. Epub 2016 Nov 28.

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

Author information

1
Hematology Research Unit Helsinki, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland.
2
Division of Hematology, Uppsala University Hospital, Uppsala, Sweden.
3
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
4
Centre for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
5
Institut National de la Sante' et de la Recherche Medicale (INSERM), CHU de Poitiers, Poitiers, France.
6
Department of Hematology, Umeå University Hospital, Umeå, Sweden.
7
Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
8
Department of Hematology, Linköping University Hospital, Linköping, Sweden.
9
Department of Hematology and Vascular Disorders, Skåne University Hospital, Lund, Sweden.
10
Department of Hematology, University Hospital, Örebro, Sweden.
11
Department of Medicine, Division of Hematology, Karolinska University Hospital, Stockholm, Sweden.
12
Department of Hematology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
13
Department of Hemato-oncology, Stavanger University hospital, Stavanger, Norway.
14
Department of Clinical Genetics, Skåne University Hospital, Lund, Sweden.
15
Finnish Red Cross Blood Service, Research and Development, Helsinki, Finland.
16
III. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany.
17
Inserm U1035, Université Bordeaux Segalen, Bordeaux, France.
18
Department of Hematology, St Olavs University Hospital, Trondheim, Norway.
19
Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland.

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 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.

PMID:
27890936
PMCID:
PMC5420794
DOI:
10.1038/leu.2016.360
[Indexed for MEDLINE]
Free PMC Article

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