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Öğe Determining expression of miRNAs that potentially regulate STAT5A and 5B in dasatinib-sensitive K562 cells(Tubitak Scientific & Technological Research Council Turkey, 2017) Yilmaz, Asu Fergun; Kaymaz, Burcin; Aktan, Cagdas; Soyer, Nur; Kosova, Buket; Gunes, Ajda; Sahin, FahriIn the era of tyrosine kinase inhibitors, resistance still constitutes a problem in chronic myeloid leukemia (CML) patients; thus, new pathway-specific inhibitors like miRNAs have become important in the treatment of refractory patients. There are no satisfying data regarding the miRNAs and anti-miRNA treatment targeting STAT5A and 5B. In this study, we first researched the effect of dasatinib on apoptosis in the CML cell line K562. The expressions of miRNAs possibly targeting both STAT5A and 5B were then determined. The down-and upregulation of the miRNAs were compared using the Delta Delta CT method. At the last stage of the study, we used a new primer probe in order to validate the results. The level of hsa-miR-940 was decreased 4.4 times and the levels of hsa-miR-527 and hsa-miR-518a-5p were increased 12.1 and 8 times, respectively, in the dasatinib-treated group when compared to the control group. We detected similar results in the validation step. As a conclusion, we determined the expression profiles of miRNAs targeting STAT5A and 5B that had an important role in the pathogenesis of CML. The data obtained could lead to determining new therapeutic targets for CML patients.Öğe Efficacy and safety of ruxolitinib in patients with myelofibrosis: a retrospective and multicenter experience in Turkey(Tubitak Scientific & Technological Research Council Turkey, 2021) Soyer, Nur; Ali, Ridvan; Turgut, Mehmet; Haznedaroglu, Ibrahim C.; Yilmaz, Fergun; Aydogdu, Ismet; Pir, AliBackground/aim: The aim of this study is to assess the efficacy and safety of ruxolitinib in patients with myelofibrosis. Materials and methods: From 15 centers, 176 patients (53.4% male, 46.6% female) were retrospectively evaluated. Results: The median age at ruxolitinib initiation was 62 (28-87) and 100 (56.8%) of all were diagnosed as PMF. Constitutional symptoms were observed in 84.7%. The median initiation dose of ruxolitinib was 30 mg (10-40). Dose change was made in 69 (39.2%) patients. Forty seven (35.6%) and 20 (15.2%) of 132 patients had hematological and nonhematological adverse events, respectively. The mean spleen sizes before and after ruxolitinib treatment were 219.67 +/- 46.79 mm versus 199.49 +/- 40.95 mm, respectively (p < 0.001). There was no correlation between baseline features and subsequent spleen response. Overall survival at 1-year was 89.5% and the median follow up was 10 (1-55) months. We could not show any relationship between survival and reduction in spleen size (p = 0.73). Conclusion: We found ruxolitinib to be safe, well tolerated, and effective in real-life clinical practice in Turkey. Ruxolitinib dose titration can provide better responses in terms of not only clinical benefit but also for long term of ruxolitinib treatment.Öğe Extramedullary Relapse in a CML Patient after Allogeneic Stem Cell Transplantation(Hindawi Ltd, 2017) Yilmaz, Asu Fergun; Soyer, Nur; Ozsan, Nazan; Cagirgan, Seckin; Gunes, Ajda; Comert, Melda; Sahin, FahriMyeloid or granulocytic sarcoma (GS) is a tumoral lesion consisting of immature granulocytic cells. It is a rare entity during the course of CML patients especially after allogeneic stem cell transplantation (SCT). Relapse without bone marrow involvement is much rarer. We report a case of CML patient who relapsed with isolated granulocytic sarcoma after allogeneic SCT during cytogenetic and molecular remission. 28-year-old male was diagnosed as CML and allogeneic SCT was performed because of refractory disease to tyrosine kinase inhibitors. Complete cytogenetic and molecular response was achieved after allogeneic SCT followed by dasatinib treatment. Approximately 5 years after the transplantation, very rapidly progressive lesion was documented and diagnosed as GS although he was at molecular and cytogenetic remission. The patient died during chemotherapy due to sepsis. GS relapse after allogeneic SCT is a very rare type of relapse in CML patients with molecular and cytogenetic remission. Since it is a very aggressive disease with a poor prognosis, combined chemoradiotherapies with other possible options like DLI or second allogeneic SCT should be considered as soon as the diagnosis is confirmed.Öğe Hematopoietic Stem Cell Transplantation for Patients with Paroxysmal Nocturnal Hemoglobinuria with or without Aplastic Anemia: A Multicenter Turkish Experience(Galenos Yayincilik, 2021) Yilmaz, Fergun; Soyer, Nur; Seval, Guldane Cengiz; Bozdag, Sinem Civriz; Topcuoglu, Pervin; Unal, Ali; Kaynar, LeylagulObjective: Although inhibition of the complement system at different steps is a promising therapy modality in patients with paroxysmal nocturnal hemoglobinuria (PNH), allogeneic hematopoietic stem cell transplantation (HCT) is still the only curative therapy, especially for patients with intractable hemolysis or bone marrow failure. The aim of this study is to evaluate the outcomes of allogeneic HCT in PNH patients with aplastic anemia (PNH-AA) or without. Materials and Methods: Thirty-five PNH/PNH-AA patients who were treated with allogeneic HCT in 10 transplantation centers in Turkey were retrospectively analyzed. Results: Sixteen (45.7%) and 19 (54.3%) patients were diagnosed with classical PNH and PNH-AA, respectively. The median age of the patients was 32 (18-51) years. The 2-year overall survival (OS) rate and rate of graft-versus-host disease-free, failure-free survival (GFFS) was 81.2% and 78.1%, respectively. The 2-year OS in cases of classical PNH and PNH-AA was 81.3% and 79.9%, respectively (p=0.87), and 2-year GFFS in cases of PNH and PNH-AA was 79% and 76% (p=0.977), without statistical significance. The OS and GFFS rates also did not differ between transplantations with matched sibling donors (MSDs) and matched unrelated donors (MUDs). Conclusion: Allogeneic HCT with MSDs or MUDS is a good option for selected patients with classical PNH and PNH-AA. In particular, patients with debilitating and refractory hemolysis and patients with bone marrow failure might form an excellent group of candidates for allogeneic HCT.Öğe Incidence and risk factors for hepatic sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation: A retrospective multicenter study of Turkish hematology research and education group (ThREG)(Pergamon-Elsevier Science Ltd, 2020) Soyer, Nur; Gunduz, Mehmet; Tekgunduz, Emre; Deveci, Burak; Ozdogu, Hakan; Sahin, Handan Haydaroglu; Turak, Esra ErmisHepatic sinusoidal obstruction syndrome (HSOS) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the incidence, risk factors, treatment and survival for HSOS after allo-HSCT in Turkey. We also reported our experience of defibrotide (DF) for HSOS prophylaxis in high-risk (HR) patients. Across Turkey, 1153 patients from 10 centers were enrolled in the study. We evaluated the medical records of patients who were treated with allo-SCT between January 2012 and December 2015. The study included 1153 patients (687 males/466 females) with median age of 38 (15 - 71) years. The incidence of HSOS was 7.5 % (n = 86). The incidences of HSOS in the HR/DF +, HR/DF- and standard risk (SR) group were 8%, 66.7 % and 6.2 %, respectively. The rate of HSOS development was not statistically different between HR/DF + and SR group (p = 0.237). HSOS prophylaxis (defibrotide) was significantly decreased HSOS-related mortality (p = 0.004). The incidence of HSOS was found similar to literature in this large Turkish cohort. Defibrotide prophylaxis appears to be associated with low incidence of HSOS development and reduced HSOS-related mortality. Although these results are promising, future studies are needed to support the efficacy of defibrotide prophylaxis in patients with risk of HSOS.Öğe Incidence and risk factors for hepatic sinusoidal obstruction syndrome after allogeneic transplantation: Retrospective multicenter study of Turkish hematology research and education group (THREG), updated data(Nature Publishing Group, 2019) Soyer, Nur; Gunduz, Mehmet; Tekgunduz, Emre; Deveci, Burak; Ozdogu, Hakan; Sahin, Handan Haydaroglu; Turak, Esra Ermis[Abstract Not Available]Öğe Multicenter Retrospective Analysis of Turkish Patients with Chronic Myeloproliferative Neoplasms(Galenos Yayincilik, 2017) Soyer, Nur; Haznedaroglu, Ibrahim C.; Comert, Melda; Cekdemir, Demet; Yilmaz, Mehmet; Unal, Ali; Cagliyan, GulsumObjective: Chronic myeloproliferative neoplasms (CMPNs) that include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are Philadelphia-negative malignancies characterized by a clonal proliferation of one or several lineages. The aim of this report was to determine the demographic features, disease characteristics, treatment strategies, and survival rates of patients with CMPNs in Turkey. Materials and Methods: Across all of Turkey, 9 centers were enrolled in the study. We retrospectively evaluated 708 CMPN patients' results including 390 with ET, 213 with PV, and 105 with PMF. Results: The JAK2V617F mutation was found positive in 86% of patients with PV, in 51.5% of patients with ET, and in 50.4% of patients with PMF. Thrombosis and bleeding at diagnosis occurred in 20.6% and 7.5% of PV patients, 15.1% and 9% of ET patients, and 9.5% and 10.4% of PMF patients, respectively. Six hundred and eight patients (85.9%) received cytoreductive therapy. The most commonly used drug was hydroxyurea (89.6%). Leukemic and fibrotic transformations occurred at rates of 0.6% and 13.2%. The estimated overall survival in PV, ET, and PMF patients was 89.7%, 85%, and 82.5% at 10 years, respectively. There were no significant differences between survival in ET, PV, and PMF patients at 10 years. Conclusion: Our patients' results are generally compatible with the literature findings, except for the relatively high survival rate in PMF patients. Hydroxyurea was the most commonly used cytoreductive therapy. Our study reflects the demographic features, patient characteristics, treatments, and survival rates of Turkish CMPN patients.
