Browsing by Author "Unal, Ekrem"

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Alantolactone Ameliorates Graft Versus Host Disease in Mice
(Elsevier, 2024) Odabas, Gul Pelin; Aslan, Kubra; Suna, Pinar Alisan; Kendirli, Perihan Kader; Erdem, Serife; Cakir, Mustafa; Unal, Ekrem
The anti-inflammatory and immunosuppressive drugs which are used in the treatment of Graft-versus-Host Disease (GVHD) have limited effects in controlling the severity of the disease. In this study, we aimed to investigate the prophylactic effect of Alantolactone (ALT) in a murine model of experimental GVHD. The study included 4 BALB/c groups as hosts: Naive (n = 7), Control GVHD (n = 16), ALT-GVHD (n = 16), and Syngeneic transplantation (n = 10). Busulfan (20 mg/kg/day) for 4 days followed by cyclophosphamide (100 mg/kg/day) were administered for conditioning. Allogeneic transplantation was performed with cells collected from mismatched female C57BL/6, and GVHD development was monitored by histological and flow cytometric assays. Additionally, liver biopsies were taken from GVHD patient volunteers between ages 2-18 (n = 4) and non-GVHD patients between ages 2-50 (n = 5) and cultured ex vivo with ALT, and the supernatants were used for ELISA. ALT significantly ameliorated histopathological scores of the GVHD and improved GVHD clinical scores. CD8+ T cells were shown to be reduced after ALT treatment. More importantly, ALT treatment skewed T cells to a more naive phenotype (CD62L+ CD44-). ALT did not alter Treg cell number or frequency. ALT treatment appears to suppress myeloid cell lineage (CD11c+). Consistent with reduced myeloid lineage, liver and small intestine levels of GM-CSF were reduced in ALT-treated mice. IL-6 gene expression was significantly reduced in the intestinal tissue. Ex vivo ALT-treated liver biopsy samples from GVHD patients showed a trend of decrease in proinflammatory cytokines but there was no statistical significance. Collectively, the data indicated that ALT may have immunomodulatory actions in a preclinical murine GVHD model.
Clinical Spectrum of Primary Hemophagocytic Lymphohistiocytosis: Experience of Reference Centers in Central and Southeast Anatolia
(Springer, 2024) Akyol, Sefika; Yilmaz, Ebru; Tokgoz, Huseyin; Karaman, Kamuran; Pekpak, Esra; Ozcan, Alper; Unal, Ekrem
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease, with a high mortality if left untreated. In addition, the disease has unique diagnostic challenges. Therefore, despite the existing guidelines on management, current clinical practice data is informative on the course and outcome. Herein, a retrospective chart review study was conducted through the collaboration of six centers, located in central and southeastern Turkiye. The demographical data, laboratory results, and treatment outcomes were evaluated. Eighty-three patients were enrolled in the study. The mean age was 2 years, whereas the median age was 8 months with a range of a minimum of 1 week and a maximum of 12.6 years. Consanguineous marriage, history of sibling death, and familial history of similar disease were determined in 72.2% (n:60), 34.9% (n:29), and 39.8% (n:33) of the patients, respectively. The most common presentation was fever, followed by hepatosplenomegaly on admission. Disease-causing familial HLH variants were identified in 60.2% (n:50) of the patients. Hematopoietic stem cell transplantation (HSCT) was performed in 39.7% (n:33) of the cohort. The 2-year overall survival (OS) rate was 62.4% for the whole group. Comparing the patients who received HSCT and those who did not; the HSCT group had a 2-year OS of 84.7%, which was significantly better than patients who did not receive HSCT had a 2-year OS of 47.1% (p:0.001). Despite the improvement in HLH diagnostics and treatment options over the last decade, early death remains a leading problem for the survival of these patients. Therefore, appropriate assessment of the patients in experienced centers and HSCT are pivotal for better outcomes.
The Number and Activity of Cd3+tcr Vα7.2+cd161+< Cells Are Increased in Children With Acute Rheumatic Fever
(Elsevier Ireland Ltd, 2021) Ozkaya, Mehmet; Baykan, Ali; Cakir, Mustafa; Vural, Cagdas; Sunkak, Suleyman; Unal, Ekrem; Eken, Ahmet
Background: Acute rheumatic fever (ARF) is an autoimmune disease caused by group A beta-hemolytic streptococci (GAS) and may develop into rheumatic heart disease (RHD). The pathogenesis of ARF and RHD involves molecular mimicry and antibody-mediated mechanisms. T cell involvement is described in various stages of the disease. Mucosal associated invariant T (MATT) cells are enriched at the mucosa and are present in the blood and may be activated by GAS. Methods: In this study, we investigated the quantity and activity of CD3(+) TCRV alpha 7.2(+) CD161(+) cells in the active and recovered ARF patients and healthy controls. Twenty newly diagnosed, 20 recovered-ARF children, and 20 healthy controls were enrolled in the study. Peripheral blood (PB) mononuclear cells were isolated by Ficoll-Paque density gradient. CD4(+) CD4(-) subsets of CD3(+) TCRV alpha 7.2(+) CD161(+) cells and IFN-gamma and TNF-alpha production were quantified by Flow cytometry. Results: Acute and recovered ARF patients had significantly elevated the number of CD3(+) TCRV alpha 7.2(+) CD161(+) cells in their PB. Both CD4(+) and CD4(-) subsets were increased. Moreover, total cell numbers were significantly higher in the recovered patients PB compared with active ARE patients. In addition, CD3(+) TCRV alpha 7.2(+) CD161(+) cells in both acute and recovered patients produced significantly more IFN-gamma and TNF-alpha. Non-MALT total CD3(+) T cell, CD4(+) and CD4(-) T cell subsets were also increased in active and recovered ARF patients and they also produced more IFN-gamma and TNF-alpha. Conclusion: Our data reveal that CD3(+) TCRV alpha 7.2(+) CD161(+) cells are elevated and actively producing IFN-gamma and TNF-alpha in acute and recovered ARF patients and may contribute to ARF pathology. (C) 2021 Elsevier B.V. All rights reserved.
Rare Coagulation Factor Deficiencies: Multicenter Experience With 188 Cases
(Istanbul Univ, 2023) Gok, Veysel; Sahinoglu, Esra Pekpak; Tokgoz, Hueseyin; Mutlu, Fatma Turkan; Acipayam, Can; Karaman, Kamuran; Unal, Ekrem
Objective: Rare factor deficiencies are a group of autosomal recessive bleeding disorders (with the exception of dysfibrinogenemia), which are characterized by the deficiency or dysfunction of one or more coagulation factors (F)I, FII, FV, FV+FVIII, FVII, FX, FXI, FXII, and FXIII. Materials and Methods: 188 patients with a rare factor deficiency from seven distinct pediatric hematology centers in Turkey were obtained for the study. Results: 60 (31.9%) patients had a family history of bleeding. Consanguinity was detected in 85 patients (45.2%). 128 patients (68.1%) were symptomatic; the most common bleeding symptom was epistaxis (34.6%) and followed by the bleeding of skin (19.1%), oral cavity (16.1%), soft tissue (8%), central nervous system (CNS) (6.2%), uterine (4.9%), joint (3.7%), gastrointestinal system (GIS) (3.7%), and urinary system (US) (3.7%). The first bleeding sites consist of nose (39%), CNS (10.9%), oral cavity (10.9%), skin (10.9%), umbilical cord (10.2%), GIS (5.5%), US (5.5%), heel (4.7%), and musculoskeletal system (2.3%). CNS hemorrhage was the most common in fibrinogen (n:4), FVII (n:6), and FX (n:2) deficiency, umbilical cord bleeding was the most common in fibrinogen (n:3) and FXIII (n:7) deficiency, heel bleeding was frequently seen in fibrinogen (n:6) deficiency. The life-threatening bleedings were CNS (n:27, 77.1%), GIS (n:7, 20%), and iliopsoas (n:1, 2.9%), respectively. The reasons leading to the diagnosis were bleeding (57.4%), preoperative screening (15.4%), incidental (15.4%), family history (6.4%), and postoperative bleeding (5.3%). 2/5 FXII deficiency patients had mild bleeding symptoms. Conclusion: As bleeding disorders are somehow a rare group of disorder, early diagnosis and treatment are critical to reduce the high morbidity and mortality.
Rituximab in Pediatric B-Cell Non-Hodgkin Lymphoma: Clinical Outcomes and Prognostic Implications
(Galenos Publ House, 2025) Akyol, Sefika; Guzel, Turan; Ozcan, Alper; Karaman, Serap; Orhan, Mehmet Fatih; Uzel, Veysiye Hulya; Unal, Ekrem
Objective: B-cell Non-Hodgkin Lymphoma (B-NHL) is an aggressive malignancy in children requiring prompt multidisciplinary management. This retrospective cohort study aims to evaluate the clinical characteristics, treatment outcomes, and impact of rituximab (RTX) in pediatric B-NHL patients. Methods: We retrospectively analyzed 62 pediatric B-NHL patients treated at tertiary centers. Patient demographics, clinical presentation, histopathological subtypes, disease stage, treatment regimens, and survival outcomes were assessed. Event-free survival (EFS) and overall survival (OS) rates were analyzed based on lactate dehydrogenase (LDH) levels and RTX administration. Results: The mean age at diagnosis was 8.73 +/- 4.3 years, with a male predominance (79%). The most common histological subtype was Burkitt lymphoma (BL) (53.2%), followed by diffuse large B-cell lymphoma (DLBCL) (33.8%). Advanced-stage disease (III-IV) was observed in 74.1% of cases. RTX was administered in 72.5% of patients, with a mean of 5.1 +/- 2.7 doses. Febrile neutropenia (FEN) was noted in 74.1%, with intensive care unit (ICU) admission required for seven patients. Mortality was observed in 12 (19.3%) patients, including all patients with primary immunodeficiency (PID). The 5-year EFS for the entire cohort was 67.2%, and OS was 81.3%. Patients with LDH <400 U/L had superior 5-year EFS (88.9%) and OS (96.3%) compared to those with LDH >400 U/L (EFS: 49.6%, OS: 70.7%; p=0.004 and p=0.015, respectively). In RTX-treated patients without PID, EFS was 76.5% versus 73.2% in those without RTX, but the difference was not statistically significant (p=0.53). Conclusions: Although not statistically significant, EFS was found to be higher in the RTX-treated group, suggesting that adding RTX to standard chemotherapy regimens may improve survival, particularly for high-risk patients, though its benefit in low-risk cases remains uncertain. Despite improved survival, patients with PID had poor outcomes, likely due to increased infections and disseminated disease. Risk-adapted, targeted treatment strategies are essential for optimizing outcomes in pediatric B-NHL. Further large-scale, randomized controlled trials are needed to confirm the efficacy of RTX in different risk groups and to optimize treatment regimens for pediatric B-NHL.