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Öğe Expression of survivin and its splice variants in pediatric acute lymphoblastic leukemia(Mary Ann Liebert, Inc, 2018) Eren-Keleş, Efsun; Karabulut, Halil Gürhan; Çakmaklı, Hasan Fatih; Adaklı Aksoy, Başak; Köse, Serdar Kenan; Uğur-Dinçaslan, Handan; Yavuz, Gülsan; Ertem, Mehmet; Tükün, AjlanAims: Survivin is involved in the inhibition of apoptosis and the regulation of cell division. In addition to wild-type survivin (survivin-wt), at least four splice variants with differential functions (Delta Ex3 and 3B antiapoptotic, and 2 alpha and 2B proapoptotic) have been identified. Survivin is highly expressed in several cancers, including hematological malignancies. Although acute lymphoblastic leukemia (ALL) is the most frequent malignancy in children, studies that investigated survivin expression in ALL are limited, and there is no study on 3B and 2 alpha expression in ALL. Therefore the expression of survivin-wt and its splice variants was investigated in pediatric B-cell ALL patients. Materials and Methods: The expression of survivin-wt and its four splice variants was investigated by quantitative real-time polymerase chain reaction in archival RNA samples of 35 pediatric B-cell ALL patients. Patients were divided into high- and standard-risk groups according to age, white blood cell count, extramedullary involvement, and genetic risk factors; expression of survivin variants was compared between these two risk groups. Results: We found that the ratio of survivin-Delta Ex3/wild type (WT) expression was higher in the low-risk group than in the high-risk group. Conclusion: Comparative analysis between the high- and low-risk B-cell ALL groups indicated that survivin-Delta Ex3/WT expression ratio could potentially be used in risk classification for pediatric B-cell ALL.Öğe Prognostic factors for survival in children who relapsed after allogeneic hematopoietic stem cell transplantation for acute leukemia(2020) Hazar, Volkan; Tezcan Karasu, Gülsün; Öztürk, Gülyüz; Küpesiz, Alphan; Aksoylar, Serap; Özbek, Namık; Uygun, Vedat; İleri, Talia; Okur, Fatma Visal; Koçak, Ülker; Çakı Kılıç, Suar; Akçay, Arzu; Güler, Elif; Kansoy, Savaş; Karakükcü, Musa; Bayram, İbrahim; Aksu , Tekin; Yeşilipek, Akif; Karagün, Barbaros Şahin; Yılmaz, Şebnem; Ertem, Mehmet; Uçkan, Duygu; Fışgın, Tunç; Gürsel, Orhan; Yaman, Yöntem; Bozkurt, Ceyhun; Gökçe, MügeBackground: Post-transplant relapse has a dismal prognosis in children with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Data on risk factors, treatment options, and outcomes are limited. Procedure: In this retrospective multicenter study in which a questionnaire was sent to all pediatric transplant centers reporting relapse after allo-HSCT for a cohort of 938 children with acute leukemia, we analyzed 255 children with relapse of acute leukemia after their first allo-HSCT. Results: The median interval from transplantation to relapse was 180 days, and the median follow-up from relapse to the last follow-up was 1844 days. The 3-year overall survival (OS) rate was 12.0%. The main cause of death was disease progression or subsequent relapse (82.6%). The majority of children received salvage treatment with curative intent without a second HSCT (67.8%), 22.0% of children underwent a second allo-HSCT, and 10.2% received palliative therapy. Isolated extramedullary relapse (hazard ratio (HR): 0.607, P = .011) and relapse earlier than 365 days post-transplantation (HR: 2.101, P < .001 for 0-180 days; HR: 1.522, P = .041 for 181-365 days) were found in multivariate analysis to be significant prognostic factors for outcome. The type of salvage therapy in chemosensitive relapse was identified as a significant prognostic factor for OS. Conclusion: A salvage approach with curative intent may be considered for patients with post-transplant relapse, even if they relapse in the first year post-transplantation. For sustainable remission, a second allo-HSCT may be recommended for patients who achieve complete remission after reinduction treatment.