Contributions
Abstract: EP656
Type: E-Poster Presentation
Session title: Chronic myeloid leukemia - Biology & Translational Research
Background
Recent studies have shown that approximately 50% of chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitor (TKI) with a sustained deep molecular response (DMR) can acquire treatment free survival (TFR), meaning without molecular relapse (MR), and that prior interferon (IFN) treatment and relatively high natural killer (NK) cell levels at and after TKI discontinuation are associated with TFR. Moreover, we recently reported that post-TKI discontinuation IFN treatment could prevent MR.
Aims
To clarify the possible mechanism of TFR in CML patients, here we evaluated whether NK cells are associated with MR in patients with CML, and investigated the effects of post-TKI discontinuation IFN treatment on lymphocyte subsets.
Methods
Part of patients with CML in our previous study of INF-α post TKI discontinuation following a DMR were included in this patient population. After immunophenotyping, the associations between lymphocyte and NK cell subsets and MR after TKI discontinuation were analyzed in the subset of patients who did not receive IFN-α and the effects of IFN-α on these same cell subsets were evaluated in those who did.
Results
Thirty-four patients measuring blood lymphocyte subclasses were included in this study. The median follow-up time was 32 (13-67) months. After TKI treatment discontinuation, 12 patients with 0.0032% < BCR-ABL1IS ≤ 0.1% received IFN-α treatment, three (25%) of which experienced protocol-defined molecular relapse (BCR-ABL1IS > 0.1%); 22 patients did not receive IFN-α treatment, 9 of whom (37.5%) eventually experienced MR. In the 22 patients who did not receive IFN therapy, there were no significant differences in Tregs or NK cells at TKI discontinuation between the nonrelapsed and relapsed patients. At one month after TKI discontinuation, the nonrelapsed patients showed a significantly higher proportion and count of NK cells than the relapsed patients (median counts and ranges of 529/mm3, 346-827 and 279/mm3, 45-645), respectively) (p=0.016). In particular, the proportion and count of CD56dim NK cells were significantly higher in the nonrelapsed patients (median: 29.92% (range: 7.42%>48.59%) and median: 467/mm3 (range: 200-955), respectively) than in the relapsed patients (median: 16.01% (range: 2.09%>31.46%) and median: 362/mm3 (range: 58-438), respectively) (p=0.017 and p=0.079, respectively). In contrast, at one month after TKI discontinuation, the nonrelapsed patients showed significantly lower proportions and counts of CD4+ T cells and CD4+CD25+CD127low/- Tregs than the relapsed patients. In the 12 patients who received IFN-α treatment, the level of CD56bright NK cells was increased significantly after both 3 and 6 months of IFN-α treatment.
Conclusion
NK cells, especially cytotoxic CD56dim NK cells, are associated with MR after TKI discontinuation in CML patients. Additionally, IFN-α treatment can gradually increase the level of CD56bright NK cells in CML patients.
Keyword(s): Chronic myeloid leukemia, Interferon alpha, NK cell, Treatment-free remission
Abstract: EP656
Type: E-Poster Presentation
Session title: Chronic myeloid leukemia - Biology & Translational Research
Background
Recent studies have shown that approximately 50% of chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitor (TKI) with a sustained deep molecular response (DMR) can acquire treatment free survival (TFR), meaning without molecular relapse (MR), and that prior interferon (IFN) treatment and relatively high natural killer (NK) cell levels at and after TKI discontinuation are associated with TFR. Moreover, we recently reported that post-TKI discontinuation IFN treatment could prevent MR.
Aims
To clarify the possible mechanism of TFR in CML patients, here we evaluated whether NK cells are associated with MR in patients with CML, and investigated the effects of post-TKI discontinuation IFN treatment on lymphocyte subsets.
Methods
Part of patients with CML in our previous study of INF-α post TKI discontinuation following a DMR were included in this patient population. After immunophenotyping, the associations between lymphocyte and NK cell subsets and MR after TKI discontinuation were analyzed in the subset of patients who did not receive IFN-α and the effects of IFN-α on these same cell subsets were evaluated in those who did.
Results
Thirty-four patients measuring blood lymphocyte subclasses were included in this study. The median follow-up time was 32 (13-67) months. After TKI treatment discontinuation, 12 patients with 0.0032% < BCR-ABL1IS ≤ 0.1% received IFN-α treatment, three (25%) of which experienced protocol-defined molecular relapse (BCR-ABL1IS > 0.1%); 22 patients did not receive IFN-α treatment, 9 of whom (37.5%) eventually experienced MR. In the 22 patients who did not receive IFN therapy, there were no significant differences in Tregs or NK cells at TKI discontinuation between the nonrelapsed and relapsed patients. At one month after TKI discontinuation, the nonrelapsed patients showed a significantly higher proportion and count of NK cells than the relapsed patients (median counts and ranges of 529/mm3, 346-827 and 279/mm3, 45-645), respectively) (p=0.016). In particular, the proportion and count of CD56dim NK cells were significantly higher in the nonrelapsed patients (median: 29.92% (range: 7.42%>48.59%) and median: 467/mm3 (range: 200-955), respectively) than in the relapsed patients (median: 16.01% (range: 2.09%>31.46%) and median: 362/mm3 (range: 58-438), respectively) (p=0.017 and p=0.079, respectively). In contrast, at one month after TKI discontinuation, the nonrelapsed patients showed significantly lower proportions and counts of CD4+ T cells and CD4+CD25+CD127low/- Tregs than the relapsed patients. In the 12 patients who received IFN-α treatment, the level of CD56bright NK cells was increased significantly after both 3 and 6 months of IFN-α treatment.
Conclusion
NK cells, especially cytotoxic CD56dim NK cells, are associated with MR after TKI discontinuation in CML patients. Additionally, IFN-α treatment can gradually increase the level of CD56bright NK cells in CML patients.
Keyword(s): Chronic myeloid leukemia, Interferon alpha, NK cell, Treatment-free remission