Contributions
Abstract: PB2090
Type: Publication Only
Background
Since introduction of azacytidine therapy for high risk myelodysplastic syndromes (MDS) several attempts have been made to define predicitive and prognostic factors in this patient cohort. Cytokines and adhesion molecules have been studied as markers of immune system activation in many diseases including MDS and acute myeloid leukemia (AML). Further knowledge gained from baseline cytokine levels assessment may help to improve treatment outcomes.
Aims
The aim of this study is to evaluate baseline levels of selected cytokines and soluble adhesion molecules and their relationship to azacytidine therapy response.
Methods
Baseline serum levels of 19 MDS patients, age 70.7 ± 3.5 years, median 72 years, were collected prior to azacytidine therapy in the period 2015 – 2017. These patients were not candidates for intensive chemotherapy or allogeneic stem cell transplantation. All patients were treated with azacytidine 75mg/m2 per day for 7 consecutive working days. Dose reduction was applied when necessary. Two subgroups were identified according to response to therapy within 6 cycles. Age, IPSS, normal karyotype, complex karyotype and bone marrow blast cell infiltration over 15% were variables included into analysis.
We evaluated serum levels of the following 17 analytes: interleukins (IL-1α, IL-1β, IL-2,
IL-4, IL-6, IL-8, IL-10), Epidermal Growth Factor (EGF), Interferon-γ, Monocyte Chemotactic Protein-1 (MCP-1), Tumor Necrosis Factor-α (TNF-α), Vascular Endothelial Growth Factor (VEGF), E-selectin (E-SEL), P-selectin (P-SEL), L-selectin (L-SEL), Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1). All biomarkers were measured by biochip array technology on Evidence Investigator analyzer (Randox). Statistical analysis was performed in STATISTICA 2.0.
Results
Based on response to azacytidine therapy, the subgroups of responders (n = 9, 47%) and non-responders (n = 10, 53%) were identified. CR was achieved in 3 cases (16%). The subgroups have not differed in age, IPSS, bone marrow blast cell infiltration or frequency of normal
karyotype or complex karyotype. The responders to azacytidine had lower levels of ICAM-1 (229.08 ± 37.85 vs. 290.97 ± 45.3, P = 0.0363), E-SEL (6.16 ± 1.85 vs. 16.38 ± 9.89, P = 0.0431) and L-SEL (759.84 ± 206.74 vs. 1166.16 ± 359.83, P = 0.0383).
Conclusion
The results indicate that high risk MDS patients can be further stratified according to cancer microenvironment, which is a sine qua non for development of new treatment approaches.
We plan to analyse these cytokines and soluble adhesion molecules as possible prognostic markers in the future.
The work was supported by a long-term organisation development plan 1011 (FMHS).
Session topic: 10. Myelodysplastic syndromes – Clinical
Keyword(s): Adhesion, Azacitidine, MDS
Abstract: PB2090
Type: Publication Only
Background
Since introduction of azacytidine therapy for high risk myelodysplastic syndromes (MDS) several attempts have been made to define predicitive and prognostic factors in this patient cohort. Cytokines and adhesion molecules have been studied as markers of immune system activation in many diseases including MDS and acute myeloid leukemia (AML). Further knowledge gained from baseline cytokine levels assessment may help to improve treatment outcomes.
Aims
The aim of this study is to evaluate baseline levels of selected cytokines and soluble adhesion molecules and their relationship to azacytidine therapy response.
Methods
Baseline serum levels of 19 MDS patients, age 70.7 ± 3.5 years, median 72 years, were collected prior to azacytidine therapy in the period 2015 – 2017. These patients were not candidates for intensive chemotherapy or allogeneic stem cell transplantation. All patients were treated with azacytidine 75mg/m2 per day for 7 consecutive working days. Dose reduction was applied when necessary. Two subgroups were identified according to response to therapy within 6 cycles. Age, IPSS, normal karyotype, complex karyotype and bone marrow blast cell infiltration over 15% were variables included into analysis.
We evaluated serum levels of the following 17 analytes: interleukins (IL-1α, IL-1β, IL-2,
IL-4, IL-6, IL-8, IL-10), Epidermal Growth Factor (EGF), Interferon-γ, Monocyte Chemotactic Protein-1 (MCP-1), Tumor Necrosis Factor-α (TNF-α), Vascular Endothelial Growth Factor (VEGF), E-selectin (E-SEL), P-selectin (P-SEL), L-selectin (L-SEL), Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1). All biomarkers were measured by biochip array technology on Evidence Investigator analyzer (Randox). Statistical analysis was performed in STATISTICA 2.0.
Results
Based on response to azacytidine therapy, the subgroups of responders (n = 9, 47%) and non-responders (n = 10, 53%) were identified. CR was achieved in 3 cases (16%). The subgroups have not differed in age, IPSS, bone marrow blast cell infiltration or frequency of normal
karyotype or complex karyotype. The responders to azacytidine had lower levels of ICAM-1 (229.08 ± 37.85 vs. 290.97 ± 45.3, P = 0.0363), E-SEL (6.16 ± 1.85 vs. 16.38 ± 9.89, P = 0.0431) and L-SEL (759.84 ± 206.74 vs. 1166.16 ± 359.83, P = 0.0383).
Conclusion
The results indicate that high risk MDS patients can be further stratified according to cancer microenvironment, which is a sine qua non for development of new treatment approaches.
We plan to analyse these cytokines and soluble adhesion molecules as possible prognostic markers in the future.
The work was supported by a long-term organisation development plan 1011 (FMHS).
Session topic: 10. Myelodysplastic syndromes – Clinical
Keyword(s): Adhesion, Azacitidine, MDS