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INTERLEUKIN-6 AND ITS RELATION TO CLINICAL AND LABORATORY CHARACTERISTICS OF PATIENTS WITH MYELOFIBROSIS
Author(s): ,
Stela Dimitrova
Affiliations:
Clinic of Hematology,UMHAT Sveta Marina Varna,Varna,Bulgaria;Medical University,Varna,Bulgaria
Ilina Micheva
Affiliations:
Clinic of Hematology,UMHAT Sveta Marina Varna,Varna,Bulgaria;Medical University,Varna,Bulgaria
EHA Library. Dimitrova S. 06/09/21; 324845; EP1123
Stela Dimitrova
Stela Dimitrova
Contributions
Abstract
Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP1123

Type: E-Poster Presentation

Session title: Myeloproliferative neoplasms - Clinical

Background
Myelofibrosis (MF) is a myeloproliferative disease, characterized by a heterogeneous clinical picture due to bone marrow fibrosis, ineffective extramedullary hematopoiesis and excessive splenomegaly. The pathogenesis of MF is multifactorial, determined by genetic profile of the patient, bone marrow microenvironment, response to inflammatory (cytokine) stimuli and age. Inflammatory cytokines are key mediators in the pathological relation between tumor microenvironment and the clonal hematopoiesis in MF. Interleukin-6 (IL-6) is a multifunctional, pleotropic, pro-inflammatory cytokine that is released by immune-competent cells as a result of infection and/or challenge to the immune system. It‘s a key participator in the tumor genesis of oncological and hematological neoplasms. IL-6 is involved in a number of pathophysiological mechanisms in MF development and is of major importance for the clinical manifestation, prognosis and progression of the disease.

Aims
The aim of the study is to analyze serum IL-6 levels in patients with MF and its relation to clinical and laboratory characteristics of patients.

Methods
We analyze 68 patients with MF (overt MF -27 patients, prefibrotic MF – 25 patients, post-polycythemia vera (post-PV) MF -9 patients and post-essential thrombocytemia (ET) MF- 7 patients) and 12 healthy controls. The mean age of the patients’ group is 67,7 years; male: female ratio - 1,7:1. According to the Dynamic International Prognostic Scoring System (DIPSS) 6 patients are high risk; 35 patients are intermediate 2 risk; 22 patients are intermediate 1 risk and 5 patients are low risk. According to the number of transfusions that patients receive per month: 40 patients are transfusion-independent and patients, receiving an average of 1 blood unit/month (BU/m) are 5; 2 BUs/m – 7 patients; 3 BUs/m – 4 patients; 4 BUs/m - 7 patients; 5 BUs/m - 4 patients and  > 6 BUs/m- 1 patient. Regarding treatment 26 patients are on best supportive therapy (BST); 26 patients are treated with cytoreductive treatment (Hydroxyurea-23 patients; Interferon α -3 patients) and 16 patients are treated with target therapy (Ruxolitinib). Degree of fibrosis in the bone marrow (grade 0-3), carrier of Jak2 V617F mutation, spleen size by ultrasound examination and peripheral blood count parameters (hemoglobin, leukocytes, platelets, MCV) are analyzed in all patients. We measure serum IL-6 levels by ELISA  in all patients and healthy controls according to the manufacturer's operating instructions. Statistical analysis is performed with SPSS version 20.

Results
 Levels of IL-6 are significantly higher in patients with MF compared to healthy controls (26.96 ± 46.73 pg/ml; -0.03 ± 1.68pg/ml; t = 1.99; p = 0.05). A significant difference is found between healthy controls, patients with overt MF (p = 0.036) and patients with post-PV MF (p = 0.028). IL-6 levels are significantly higher in patients with grade 3 fibrosis in comparison to the other grades (60.4 ± 77.3 pg /ml; p = 0.025). There is a strong significant correlation between IL-6 and the number of blood transfusions per month (r = 0.488; p <0.001). No correlation is found with hemoglobin, leukocyte count, MCV, spleen size, Jak2 mutation, DIPSS, symptomatic disease and treatment.

Conclusion
 IL-6 is a key mediator in the pathogenesis and clinical evolution of MF. Its involvement in the establishment of a cytokine risk model of MF, makes it a potential target for therapeutic response, control and monitoring of the disease.

Keyword(s): IL-6, Myelofibrosis

Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP1123

Type: E-Poster Presentation

Session title: Myeloproliferative neoplasms - Clinical

Background
Myelofibrosis (MF) is a myeloproliferative disease, characterized by a heterogeneous clinical picture due to bone marrow fibrosis, ineffective extramedullary hematopoiesis and excessive splenomegaly. The pathogenesis of MF is multifactorial, determined by genetic profile of the patient, bone marrow microenvironment, response to inflammatory (cytokine) stimuli and age. Inflammatory cytokines are key mediators in the pathological relation between tumor microenvironment and the clonal hematopoiesis in MF. Interleukin-6 (IL-6) is a multifunctional, pleotropic, pro-inflammatory cytokine that is released by immune-competent cells as a result of infection and/or challenge to the immune system. It‘s a key participator in the tumor genesis of oncological and hematological neoplasms. IL-6 is involved in a number of pathophysiological mechanisms in MF development and is of major importance for the clinical manifestation, prognosis and progression of the disease.

Aims
The aim of the study is to analyze serum IL-6 levels in patients with MF and its relation to clinical and laboratory characteristics of patients.

Methods
We analyze 68 patients with MF (overt MF -27 patients, prefibrotic MF – 25 patients, post-polycythemia vera (post-PV) MF -9 patients and post-essential thrombocytemia (ET) MF- 7 patients) and 12 healthy controls. The mean age of the patients’ group is 67,7 years; male: female ratio - 1,7:1. According to the Dynamic International Prognostic Scoring System (DIPSS) 6 patients are high risk; 35 patients are intermediate 2 risk; 22 patients are intermediate 1 risk and 5 patients are low risk. According to the number of transfusions that patients receive per month: 40 patients are transfusion-independent and patients, receiving an average of 1 blood unit/month (BU/m) are 5; 2 BUs/m – 7 patients; 3 BUs/m – 4 patients; 4 BUs/m - 7 patients; 5 BUs/m - 4 patients and  > 6 BUs/m- 1 patient. Regarding treatment 26 patients are on best supportive therapy (BST); 26 patients are treated with cytoreductive treatment (Hydroxyurea-23 patients; Interferon α -3 patients) and 16 patients are treated with target therapy (Ruxolitinib). Degree of fibrosis in the bone marrow (grade 0-3), carrier of Jak2 V617F mutation, spleen size by ultrasound examination and peripheral blood count parameters (hemoglobin, leukocytes, platelets, MCV) are analyzed in all patients. We measure serum IL-6 levels by ELISA  in all patients and healthy controls according to the manufacturer's operating instructions. Statistical analysis is performed with SPSS version 20.

Results
 Levels of IL-6 are significantly higher in patients with MF compared to healthy controls (26.96 ± 46.73 pg/ml; -0.03 ± 1.68pg/ml; t = 1.99; p = 0.05). A significant difference is found between healthy controls, patients with overt MF (p = 0.036) and patients with post-PV MF (p = 0.028). IL-6 levels are significantly higher in patients with grade 3 fibrosis in comparison to the other grades (60.4 ± 77.3 pg /ml; p = 0.025). There is a strong significant correlation between IL-6 and the number of blood transfusions per month (r = 0.488; p <0.001). No correlation is found with hemoglobin, leukocyte count, MCV, spleen size, Jak2 mutation, DIPSS, symptomatic disease and treatment.

Conclusion
 IL-6 is a key mediator in the pathogenesis and clinical evolution of MF. Its involvement in the establishment of a cytokine risk model of MF, makes it a potential target for therapeutic response, control and monitoring of the disease.

Keyword(s): IL-6, Myelofibrosis

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