Natural killer cell counts are associated with molecular relapse-free survival after imatinib discontinuation in chronic myeloid leukemia: the IMMUNOSTIM study.
Fiche publication
Date publication
mai 2017
Journal
Haematologica
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GUERCI-BRESLER Agnès
Tous les auteurs :
Rea D, Henry G, Khaznadar Z, Etienne G, Guilhot F, Nicolini F, Guilhot J, Rousselot P, Huguet F, Legros L, Gardembas M, Dubruille V, Guerci-Bresler A, Charbonnier A, Maloisel F, Ianotto JC, Villemagne B, Mahon FX, Moins-Teisserenc H, Dulphy N, Toubert A
Lien Pubmed
Résumé
Despite leukemic stem cell persistence, 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 displayed significantly higher numbers of natural killer-cells of the cytotoxic CD56dim subset than relapsing patients, while CD56bright natural killer cells, T-cells and their subsets did not significantly differ. Furthermore, the CD56dim natural killer-cell count was an independent prognostic factor of molecular-relapse free survival in a multivariate analysis. However, natural killer cells activating receptor expression, BCR-ABL1+ 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, natural killer-cells significantly increased 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 for natural killer-cell functional differences between patients and healthy individuals and evaluate the potential interest of immunostimulatory approaches in tyrosine kinase inhibitor discontinuation strategies.(ClinicalTrial.gov Identifier NCT00478985).
Mots clés
Cell Count, Disease-Free Survival, Humans, Imatinib Mesylate, therapeutic use, Interferon-gamma, analysis, Killer Cells, Natural, cytology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, drug therapy, Protein Kinase Inhibitors, therapeutic use, Receptors, Natural Killer Cell, analysis, Recurrence
Référence
Haematologica. 2017 May;: