@article{Delphine Rea_Guylaine Henry_Zena Khaznadar_Gabriel Etienne_François Guilhot_Franck Nicolini_Joelle Guilhot_Philippe Rousselot_Françoise Huguet_Laurence Legros_Martine Gardembas_Viviane Dubruille_Agnès Guerci-Bresler_Aude Charbonnier_Frédéric Maloisel_Jean-Christophe Ianotto_Bruno Villemagne_François-Xavier Mahon_Hélène Moins-Teisserenc_Nicolas Dulphy_Antoine Toubert_2017, place={Pavia, Italy}, title={Natural killer-cell counts are associated with molecular relapse-free survival after imatinib discontinuation in chronic myeloid leukemia: the IMMUNOSTIM study}, volume={102}, url={https://haematologica.org/article/view/8157}, DOI={10.3324/haematol.2017.165001}, abstractNote={Despite persistence of leukemic stem cells, patients with chronic myeloid leukemia who achieve and maintain deep molecular responses may successfully stop the tyrosine kinase inhibitor imatinib. However, questions remain unanswered regarding the biological basis of molecular relapse after imatinib cessation. In IMMUNOSTIM, we monitored 51 patients from the French Stop IMatinib trial for peripheral blood T cells and natural killer cells. Molecular relapse-free survival at 24 months was 45.1% (95% CI: 31.44%–58.75%). At the time of imatinib discontinuation, non-relapsing patients had significantly higher numbers of natural killer cells of the cytotoxic CD56<sup>dim</sup> subset than had relapsing patients, while CD56<sup>bright</sup> natural killer cells, T cells and their subsets did not differ significantly. Furthermore, the CD56<sup>dim</sup> natural killer-cell count was an independent prognostic factor of molecular-relapse free survival in a multivariate analysis. However, expression of natural killer-cell activating receptors, <em>BCR-ABL1</em><sup>+</sup> leukemia cell line K562-specific degranulation and cytokine-induced interferon-gamma secretion were decreased in non-relapsing and relapsing patients as compared with healthy individuals. After imatinib cessation, the natural killer-cell count increased significantly and stayed higher in non-relapsing patients than in relapsing patients, while receptor expression and functional properties remained unchanged. Altogether, our results suggest that natural killer cells may play a role in controlling leukemia-initiating cells at the origin of relapse after imatinib cessation, provided that these cells are numerous enough to compensate for their functional defects. Further research will decipher mechanisms underlying functional differences between natural killer cells from patients and healthy individuals and evaluate the potential interest of immunostimulatory approaches in tyrosine kinase inhibitor discontinuation strategies. <em>(<a href="http://ClinicalTrial.gov">ClinicalTrial.gov</a> Identifier <a class="external-ref external-ref-type-clintrialgov" href="/lookup/external-ref?link_type=CLINTRIALGOV&amp;access_num=NCT00478985&amp;atom=%2Fhaematol%2F102%2F8%2F1368.atom">NCT00478985</a>)</em&gt;}, number={8}, journal={Haematologica}, author={Delphine Rea and Guylaine Henry and Zena Khaznadar and Gabriel Etienne and François Guilhot and Franck Nicolini and Joelle Guilhot and Philippe Rousselot and Françoise Huguet and Laurence Legros and Martine Gardembas and Viviane Dubruille and Agnès Guerci-Bresler and Aude Charbonnier and Frédéric Maloisel and Jean-Christophe Ianotto and Bruno Villemagne and François-Xavier Mahon and Hélène Moins-Teisserenc and Nicolas Dulphy and Antoine Toubert}, year={2017}, month={Jul.}, pages={1368-1377} }