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).
Natural killer cell counts are associated with molecular relapse-free survival after imatinib discontinuation in chronic myeloid leukemia: the IMMUNOS
Posted 13 August 2017 - 08:01 PM
Posted 14 August 2017 - 08:58 AM
If that hypothesis is accurate (hard to say) then younger women would be far less likely to have success at cessation. That is because NK cells are suppressed during stages of the menstrual cycle and pregnancy. We have several women who post here who were diagnosed during/just after pregnancy, which might lend some credence to the theory. Also rapid expansion of leukemia may occur during pregnancy. Just some random observations to consider. Maybe birth control pills would help keep NK cells higher (unknown).
Posted 14 August 2017 - 04:57 PM
I still think there are a small number of us who had their immune response affected by high levels of stress. Why the immune response fails for the majority, no idea.
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