EHA Library - The official digital education library of European Hematology Association (EHA)

IMMUNOMODULATORY EFFECT OF DASATINIB THERAPY IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA
Author(s): ,
Maria Cioch
Affiliations:
Department of Haematooncology and Bone Marrow Transplantation,Medical University in Lublin,Lublin,Poland
,
Pawel Jarosz
Affiliations:
Department of Haematooncology and Bone Marrow Transplantation,Medical University in Lublin,Lublin,Poland
,
Dariusz Jawniak
Affiliations:
Department of Haematooncology and Bone Marrow Transplantation,Medical University in Lublin,Lublin,Poland
,
Aneta Goracy
Affiliations:
Department of Haematooncology and Bone Marrow Transplantation,Medical University in Lublin,Lublin,Poland
,
Malgorzata Wach
Affiliations:
Department of Haematooncology and Bone Marrow Transplantation,Medical University in Lublin,Lublin,Poland
,
Ewa Wasik-Szczepanek
Affiliations:
Department of Haematooncology and Bone Marrow Transplantation,Medical University in Lublin,Lublin,Poland
Marek Hus
Affiliations:
Department of Haematooncology and Bone Marrow Transplantation,Medical University in Lublin,Lublin,Poland
(Abstract release date: 05/19/16) EHA Library. Cioch M. 06/09/16; 134726; PB1826
Dr. Maria Cioch
Dr. Maria Cioch
Contributions
Abstract
Abstract: PB1826

Type: Publication Only

Background
Dasatinib is a second generation tyrosine kinase inhibitor (TKI), widely used in patients (pts) with chronic myeloid leukemia (CML), especially in failure after imatinib. The quite often side effect of dastinib is lymphocytosis and pleural effusion (PE). These phenomenons are probably connected with immunological mechanisms.

Aims
The aim of our study was  analysis of the influence of three presently used TKIs: imatinib, nilotinib and dasatinib on different populations of lymphocytes: B cells (Bc), T helper (Th), T suppressor (Ts), T regulatory (Treg), NK cells (NKc) and NKT cells (NKTc).

Methods
A total 37 pts with CML from Department of Haematology and Bone Marrow Transplantation in Lublin were recruited to this study. There were 17 pts on imatinib therapy (imatinib group; IG), 10 pts on nilotinib therapy (nilotinib group; NG) and 10 pts on dasatinib therapy (dasatinib group; DG). As control group there were 23 healthy volunteers. Material for the analysis was vein blood collected from CML pts after minimum 3 months of TKIs therapy. Blood samples were used for the evaluation of lymphocyte count and its immunophenotype to distinguish such subpopulataions as: Bc, Th, Ts, Treg, NKc and NKTc.

Results
Patients treated with dasatinib had significantly higher median number of lymphocytes in blood (3.59 G/L) compared with pts treated with nilotinib (2.31 G/L; p<0.01) and imatinib (1.93 G/L; p<0.001). The median CD19+ expression (Bc) in comparison with control group was significantly lower in DG than in IG and NG (p=0.00039). There was no significant difference in Th, Ts and NKTc antigens expression. The analysis showed that in DG there was significantly higher expression of NKc antigens (CD3-CD16+CD56+) compared with control group than in IG and NG (p<0.05). The expression of Treg antigens (Foxp3+CD4+CD25high) was significantly lower in DG compared with control group than in IG and NG (p<0.001).

Conclusion
The results of our study showed immunomodulatory effect of dasatinib therapy in pts with CML manifested by increase of lymphocyte count and NK cells and decrease of Treg and B cells. This action of dasatinib is associated with such immunological phenomenon as PE and may be considered as additional factor influencing on better clinical response.

Session topic: E-poster

Keyword(s): Chronic myeloid leukemia, Immunomodulation, Tyrosine kinase inhibitor
Abstract: PB1826

Type: Publication Only

Background
Dasatinib is a second generation tyrosine kinase inhibitor (TKI), widely used in patients (pts) with chronic myeloid leukemia (CML), especially in failure after imatinib. The quite often side effect of dastinib is lymphocytosis and pleural effusion (PE). These phenomenons are probably connected with immunological mechanisms.

Aims
The aim of our study was  analysis of the influence of three presently used TKIs: imatinib, nilotinib and dasatinib on different populations of lymphocytes: B cells (Bc), T helper (Th), T suppressor (Ts), T regulatory (Treg), NK cells (NKc) and NKT cells (NKTc).

Methods
A total 37 pts with CML from Department of Haematology and Bone Marrow Transplantation in Lublin were recruited to this study. There were 17 pts on imatinib therapy (imatinib group; IG), 10 pts on nilotinib therapy (nilotinib group; NG) and 10 pts on dasatinib therapy (dasatinib group; DG). As control group there were 23 healthy volunteers. Material for the analysis was vein blood collected from CML pts after minimum 3 months of TKIs therapy. Blood samples were used for the evaluation of lymphocyte count and its immunophenotype to distinguish such subpopulataions as: Bc, Th, Ts, Treg, NKc and NKTc.

Results
Patients treated with dasatinib had significantly higher median number of lymphocytes in blood (3.59 G/L) compared with pts treated with nilotinib (2.31 G/L; p<0.01) and imatinib (1.93 G/L; p<0.001). The median CD19+ expression (Bc) in comparison with control group was significantly lower in DG than in IG and NG (p=0.00039). There was no significant difference in Th, Ts and NKTc antigens expression. The analysis showed that in DG there was significantly higher expression of NKc antigens (CD3-CD16+CD56+) compared with control group than in IG and NG (p<0.05). The expression of Treg antigens (Foxp3+CD4+CD25high) was significantly lower in DG compared with control group than in IG and NG (p<0.001).

Conclusion
The results of our study showed immunomodulatory effect of dasatinib therapy in pts with CML manifested by increase of lymphocyte count and NK cells and decrease of Treg and B cells. This action of dasatinib is associated with such immunological phenomenon as PE and may be considered as additional factor influencing on better clinical response.

Session topic: E-poster

Keyword(s): Chronic myeloid leukemia, Immunomodulation, Tyrosine kinase inhibitor

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