Contributions
Abstract: PB1943
Type: Publication Only
Background
Chronic myeloid leukemia (CML) is characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22)], producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors (TKIs) represent the standard of care for CML patients (pts) through a direct oncokinase inhibition and well characterized immunomodulatory effects on T and NK cells. The main treatment goal is the achievement of deep molecular response (DMR), which makes disease progression highly unlikely and may even trigger discontinuation of TKIs. In recent years immunological factors are increasingly acknowledged as important variables being linked to achievement of DMR as well as maintenance of treatment-free remission in patients upon TKI discontinuation. NK cells are dysfunctional in CP CML patients at diagnosis and NK cell numbers among lymphocytes are reduced, worsening with disease progression to advanced and blast crisis phase CML.
Aims
We studied lymphocytes subsets, particularly NK cells number, in CML pts at diagnosis and at attainment of molecular response, to evaluate variations in NK cells number during the course of the disease.
Methods
81 patients (54 M, 27 F; median age: 59, range: 19-86) were evaluated. 16 pts were in Chronic Phase (CP) at diagnosis, 23 in MR3, 40 in MR4/MR4.5, 2 were resistant to TKIs. 21 pts were studied at diagnosis and at achievement of Major or Deep Molecular Response (MMR/DMR). Flow cytometry analysis was performed on peripheral blood samples using the following antibodies: CD45, CD3, CD16, CD56, CD4, CD8, CD19. Samples were acquired on the FACS CANTO II (BD Bioscences) cytometer and analyzed with BCANTO software using an immunological gate (SSC/CD45) to select lymphocytes.
Results
When we studied lymphocytes subsets at a single timepoint in all the pts, we observed a significantly lower number of NK cells in pts evaluated at diagnosis (median: 13,5% , range: 3-35% ) than in pts who were in MMR (median: 17%, range: 9-45% ) or DMR (median:19%, range: 12-49%). In 2 pts resistant to TKIs NK values were respectively 2% and 3%. In 21 pts analyzed at diagnosis and at achievement of MMR (12 pts) and DMR (8 pts), we observed a progressive increase in NK number during the course of the disease, along with a progressive reduction of BCR-ABL transcript.
Conclusion
An increased percentage of NK at diagnosis seems to correlate with a faster achievement of MMR or DMR. Our data suggest a better prognosis for all patients maintaining an higher percentage of NK during the course of the disease. Further analysis should be made considering the effect of different TKIs on the immunological state of each patient.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, Molecular response, NK cell
Abstract: PB1943
Type: Publication Only
Background
Chronic myeloid leukemia (CML) is characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 [t(9;22)], producing the Bcr-Abl oncogene. Tyrosine kinase inhibitors (TKIs) represent the standard of care for CML patients (pts) through a direct oncokinase inhibition and well characterized immunomodulatory effects on T and NK cells. The main treatment goal is the achievement of deep molecular response (DMR), which makes disease progression highly unlikely and may even trigger discontinuation of TKIs. In recent years immunological factors are increasingly acknowledged as important variables being linked to achievement of DMR as well as maintenance of treatment-free remission in patients upon TKI discontinuation. NK cells are dysfunctional in CP CML patients at diagnosis and NK cell numbers among lymphocytes are reduced, worsening with disease progression to advanced and blast crisis phase CML.
Aims
We studied lymphocytes subsets, particularly NK cells number, in CML pts at diagnosis and at attainment of molecular response, to evaluate variations in NK cells number during the course of the disease.
Methods
81 patients (54 M, 27 F; median age: 59, range: 19-86) were evaluated. 16 pts were in Chronic Phase (CP) at diagnosis, 23 in MR3, 40 in MR4/MR4.5, 2 were resistant to TKIs. 21 pts were studied at diagnosis and at achievement of Major or Deep Molecular Response (MMR/DMR). Flow cytometry analysis was performed on peripheral blood samples using the following antibodies: CD45, CD3, CD16, CD56, CD4, CD8, CD19. Samples were acquired on the FACS CANTO II (BD Bioscences) cytometer and analyzed with BCANTO software using an immunological gate (SSC/CD45) to select lymphocytes.
Results
When we studied lymphocytes subsets at a single timepoint in all the pts, we observed a significantly lower number of NK cells in pts evaluated at diagnosis (median: 13,5% , range: 3-35% ) than in pts who were in MMR (median: 17%, range: 9-45% ) or DMR (median:19%, range: 12-49%). In 2 pts resistant to TKIs NK values were respectively 2% and 3%. In 21 pts analyzed at diagnosis and at achievement of MMR (12 pts) and DMR (8 pts), we observed a progressive increase in NK number during the course of the disease, along with a progressive reduction of BCR-ABL transcript.
Conclusion
An increased percentage of NK at diagnosis seems to correlate with a faster achievement of MMR or DMR. Our data suggest a better prognosis for all patients maintaining an higher percentage of NK during the course of the disease. Further analysis should be made considering the effect of different TKIs on the immunological state of each patient.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Chronic myeloid leukemia, Molecular response, NK cell