THE ALTERATION OF IMMUNOPROFILE DURING DASATINIB TREATMENT IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA: A PROSPECTIVE OBSERVATIONAL STUDY
(Abstract release date: 05/19/16)
EHA Library. Kuno M. 06/09/16; 132655; E1106
Dr. Masatomo Kuno
Contributions
Contributions
Abstract
Abstract: E1106
Type: Eposter Presentation
Background
Some chronic myeloid leukemia (CML) patients treated with dasatinib develop lymphocytosis with an expansion of large granular lymphocytes (LGLs) and natural killer (NK) cells. The lymphocytosis is known to be related to a better response to dasatinib therapy and survival. However, it has been not elucidated whether increased lymphocytes harbor an effective immunological and/or anti-tumor activity.
Aims
The aims of this prospective study were 1) to evaluate changes of NK-cell reactivity and soluble factors and 2) immune cell counts by dasatinib therapy in treatment naive CML patients and those who were treated with dasatinib beyond the first line therapy.
Methods
Thirty patients with CML in chronic phase who started tyrosine kinase inhibitor (TKI) as the first-line treatment or switched to the other TKI were enrolled in this study between September 2010 and December 2013 at our institute. TKIs were; dasatinib (as first line n=7, beyond first line n=12), imatinib (as first line n=3), nilotinib (as first line n=2, beyond first line n=6). We analyzed peripheral blood samples collected from patients at enrollment, 1, 3, 6 and 12 months after the initiation of treatment to determine cell counts, lymphocyte subset (such as NK cells, NK-LGLs, T-LGLs and regulatory T cells) immunophenotyping by flow cytometry, NK cell activity and plasma levels of 27 soluble factors.
Results
The number of lymphocytes, NK cells, T-LGLs and NK-LGLs significantly increased in patients treated with dasatinib (all P<0.01). NK cell activity at effector to target (E: T) ratios of 10: 1 and 20: 1 significantly elevated in patients with dasatinib as the first-line treatment (P<0.01) and beyond first-line treatment (P<0.01). The levels of NK cell activity at diagnosis were below the normal level in all treatment naive CML patients and elevated above the normal level at 12 months after the dasatinib therapy in more than half of the patients. In addition, NK cell activity was significantly negatively correlated with BCR-ABL mRNA transcript levels in the dasatinib group (r= -0.304, P=0.011) but not in patients treated with imatinib or nilotinib. A significant association was found between the numbers of T-LGL before and 3 months (P<0.01), and before and 6 months after dasatinib therapy (P<0.01). There were no significant change in counts of any immune cell in patients receiving imatinib or nilotinib. Furthermore, we could not determine a type of chemokine or cytokine associated with lymphocytosis induced by the dasatinib treatment.
Conclusion
Dasatinib might increase the numbers of LGL and enhance NK-cell cytotoxicity in vivo. Dasatinib might restore the function of exhausted cytotoxic lymphocytes present already at the time of CML diagnosis. Increase in LGL counts was strongly correlated with the number of LGL before dasatinib therapy. We speculated that the number of LGL present before dasatinib therapy is potentially a prognostic factor.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Immune response, Tyrosine kinase inhibitor
Type: Eposter Presentation
Background
Some chronic myeloid leukemia (CML) patients treated with dasatinib develop lymphocytosis with an expansion of large granular lymphocytes (LGLs) and natural killer (NK) cells. The lymphocytosis is known to be related to a better response to dasatinib therapy and survival. However, it has been not elucidated whether increased lymphocytes harbor an effective immunological and/or anti-tumor activity.
Aims
The aims of this prospective study were 1) to evaluate changes of NK-cell reactivity and soluble factors and 2) immune cell counts by dasatinib therapy in treatment naive CML patients and those who were treated with dasatinib beyond the first line therapy.
Methods
Thirty patients with CML in chronic phase who started tyrosine kinase inhibitor (TKI) as the first-line treatment or switched to the other TKI were enrolled in this study between September 2010 and December 2013 at our institute. TKIs were; dasatinib (as first line n=7, beyond first line n=12), imatinib (as first line n=3), nilotinib (as first line n=2, beyond first line n=6). We analyzed peripheral blood samples collected from patients at enrollment, 1, 3, 6 and 12 months after the initiation of treatment to determine cell counts, lymphocyte subset (such as NK cells, NK-LGLs, T-LGLs and regulatory T cells) immunophenotyping by flow cytometry, NK cell activity and plasma levels of 27 soluble factors.
Results
The number of lymphocytes, NK cells, T-LGLs and NK-LGLs significantly increased in patients treated with dasatinib (all P<0.01). NK cell activity at effector to target (E: T) ratios of 10: 1 and 20: 1 significantly elevated in patients with dasatinib as the first-line treatment (P<0.01) and beyond first-line treatment (P<0.01). The levels of NK cell activity at diagnosis were below the normal level in all treatment naive CML patients and elevated above the normal level at 12 months after the dasatinib therapy in more than half of the patients. In addition, NK cell activity was significantly negatively correlated with BCR-ABL mRNA transcript levels in the dasatinib group (r= -0.304, P=0.011) but not in patients treated with imatinib or nilotinib. A significant association was found between the numbers of T-LGL before and 3 months (P<0.01), and before and 6 months after dasatinib therapy (P<0.01). There were no significant change in counts of any immune cell in patients receiving imatinib or nilotinib. Furthermore, we could not determine a type of chemokine or cytokine associated with lymphocytosis induced by the dasatinib treatment.
Conclusion
Dasatinib might increase the numbers of LGL and enhance NK-cell cytotoxicity in vivo. Dasatinib might restore the function of exhausted cytotoxic lymphocytes present already at the time of CML diagnosis. Increase in LGL counts was strongly correlated with the number of LGL before dasatinib therapy. We speculated that the number of LGL present before dasatinib therapy is potentially a prognostic factor.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Immune response, Tyrosine kinase inhibitor
Abstract: E1106
Type: Eposter Presentation
Background
Some chronic myeloid leukemia (CML) patients treated with dasatinib develop lymphocytosis with an expansion of large granular lymphocytes (LGLs) and natural killer (NK) cells. The lymphocytosis is known to be related to a better response to dasatinib therapy and survival. However, it has been not elucidated whether increased lymphocytes harbor an effective immunological and/or anti-tumor activity.
Aims
The aims of this prospective study were 1) to evaluate changes of NK-cell reactivity and soluble factors and 2) immune cell counts by dasatinib therapy in treatment naive CML patients and those who were treated with dasatinib beyond the first line therapy.
Methods
Thirty patients with CML in chronic phase who started tyrosine kinase inhibitor (TKI) as the first-line treatment or switched to the other TKI were enrolled in this study between September 2010 and December 2013 at our institute. TKIs were; dasatinib (as first line n=7, beyond first line n=12), imatinib (as first line n=3), nilotinib (as first line n=2, beyond first line n=6). We analyzed peripheral blood samples collected from patients at enrollment, 1, 3, 6 and 12 months after the initiation of treatment to determine cell counts, lymphocyte subset (such as NK cells, NK-LGLs, T-LGLs and regulatory T cells) immunophenotyping by flow cytometry, NK cell activity and plasma levels of 27 soluble factors.
Results
The number of lymphocytes, NK cells, T-LGLs and NK-LGLs significantly increased in patients treated with dasatinib (all P<0.01). NK cell activity at effector to target (E: T) ratios of 10: 1 and 20: 1 significantly elevated in patients with dasatinib as the first-line treatment (P<0.01) and beyond first-line treatment (P<0.01). The levels of NK cell activity at diagnosis were below the normal level in all treatment naive CML patients and elevated above the normal level at 12 months after the dasatinib therapy in more than half of the patients. In addition, NK cell activity was significantly negatively correlated with BCR-ABL mRNA transcript levels in the dasatinib group (r= -0.304, P=0.011) but not in patients treated with imatinib or nilotinib. A significant association was found between the numbers of T-LGL before and 3 months (P<0.01), and before and 6 months after dasatinib therapy (P<0.01). There were no significant change in counts of any immune cell in patients receiving imatinib or nilotinib. Furthermore, we could not determine a type of chemokine or cytokine associated with lymphocytosis induced by the dasatinib treatment.
Conclusion
Dasatinib might increase the numbers of LGL and enhance NK-cell cytotoxicity in vivo. Dasatinib might restore the function of exhausted cytotoxic lymphocytes present already at the time of CML diagnosis. Increase in LGL counts was strongly correlated with the number of LGL before dasatinib therapy. We speculated that the number of LGL present before dasatinib therapy is potentially a prognostic factor.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Immune response, Tyrosine kinase inhibitor
Type: Eposter Presentation
Background
Some chronic myeloid leukemia (CML) patients treated with dasatinib develop lymphocytosis with an expansion of large granular lymphocytes (LGLs) and natural killer (NK) cells. The lymphocytosis is known to be related to a better response to dasatinib therapy and survival. However, it has been not elucidated whether increased lymphocytes harbor an effective immunological and/or anti-tumor activity.
Aims
The aims of this prospective study were 1) to evaluate changes of NK-cell reactivity and soluble factors and 2) immune cell counts by dasatinib therapy in treatment naive CML patients and those who were treated with dasatinib beyond the first line therapy.
Methods
Thirty patients with CML in chronic phase who started tyrosine kinase inhibitor (TKI) as the first-line treatment or switched to the other TKI were enrolled in this study between September 2010 and December 2013 at our institute. TKIs were; dasatinib (as first line n=7, beyond first line n=12), imatinib (as first line n=3), nilotinib (as first line n=2, beyond first line n=6). We analyzed peripheral blood samples collected from patients at enrollment, 1, 3, 6 and 12 months after the initiation of treatment to determine cell counts, lymphocyte subset (such as NK cells, NK-LGLs, T-LGLs and regulatory T cells) immunophenotyping by flow cytometry, NK cell activity and plasma levels of 27 soluble factors.
Results
The number of lymphocytes, NK cells, T-LGLs and NK-LGLs significantly increased in patients treated with dasatinib (all P<0.01). NK cell activity at effector to target (E: T) ratios of 10: 1 and 20: 1 significantly elevated in patients with dasatinib as the first-line treatment (P<0.01) and beyond first-line treatment (P<0.01). The levels of NK cell activity at diagnosis were below the normal level in all treatment naive CML patients and elevated above the normal level at 12 months after the dasatinib therapy in more than half of the patients. In addition, NK cell activity was significantly negatively correlated with BCR-ABL mRNA transcript levels in the dasatinib group (r= -0.304, P=0.011) but not in patients treated with imatinib or nilotinib. A significant association was found between the numbers of T-LGL before and 3 months (P<0.01), and before and 6 months after dasatinib therapy (P<0.01). There were no significant change in counts of any immune cell in patients receiving imatinib or nilotinib. Furthermore, we could not determine a type of chemokine or cytokine associated with lymphocytosis induced by the dasatinib treatment.
Conclusion
Dasatinib might increase the numbers of LGL and enhance NK-cell cytotoxicity in vivo. Dasatinib might restore the function of exhausted cytotoxic lymphocytes present already at the time of CML diagnosis. Increase in LGL counts was strongly correlated with the number of LGL before dasatinib therapy. We speculated that the number of LGL present before dasatinib therapy is potentially a prognostic factor.
Session topic: E-poster
Keyword(s): Chronic myeloid leukemia, Immune response, Tyrosine kinase inhibitor
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