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    COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group
    (2024) Bozkurt, Ceyhun; Hazar, Volkan; Malbora, Barış; Küpesiz, Alphan; Aygüneş, Utku; Fışgın, Tunç; Karakükçü, Musa; Kuşkonmaz, Barış; Kılıç, Suar Çakı; Bayırlı, Derya; Bilir, Özlem Arman; Yalçın, Koray; Gözmen, Salih; Uygun, Vedat; Elli, Murat; Sarbay, Hakan; Küpesiz, Funda Tayfun; Şaşmaz, Hatice İlgen; Aksoy, Başak Adaklı; Yılmaz, Ebru; Okur, Fatma Visal; Tekkeşin, Funda; Yenigürbüz, Fatma Demir; Özek, Gülcihan; Atay, Abdullah Avni; Bozkaya, İkbal Ok; Çelen, Suna; Öztürkmen, Seda; Güneş, Adalet Meral; Gürsel, Orhan; Güler, Elif; Özcan, Alper; Çetinkaya, Duygu Uçkan; Aydoğdu, Selime; Özbek, Namık Yaşar; Karasu, Gülsün; Sezgin, Gülay; Doğru, Ömer; Albayrak, Davut; Öztürk, Gülyüz; Aksoylar, Serap; Daloğlu, Hayriye; Al, Işık Odaman; Evim, Melike Sezgin; Akbayram, Sinan; Öncül, Yurday; Zengin, Emine; Albayrak, Canan; Timur, Çetin; Kar, Yeter Düzenli; Çakmaklı, Hasan Fatih; Tüfekçi, Özlem; Töret, Ersin; Antmen, Bülent
    Background: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. Objectives: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection. Method: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022. Results: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality. Conclusion: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD.
  • Küçük Resim
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    Different kinetics and risk factors for ısolated extramedullary relapse after allogeneic hematopoietic stem cell transplantation in children with acute leukemia
    (Elsevier, 2021) Hazar, Volkan; Öztürk, Gülyüz; Yalçın, Koray; Uygun, Vedat; Aksoylar, Serap; Küpesiz, A.; Ok Bozkaya, İkbal; Karagün, Barbaros Şahin; İleri, Talia; Atay, Didem; Koçak, Ülker; Tezcan Karasu, Gülsün; Yeşilipek, Akif; Gökçe, Müge; Kansoy, Savaş; Tüysüz Kintrup, Gülen; Karakükçü, Musa; Visal Okur, Fatma; Ertem, Mehmet; Kaya, Zühre; Gürsel, Orhan; Yaman, Yöntem; Özbek, Namık; Antmen, Bülent; Tüfekçi, Özlem; Albayrak, Canan; Adaklı Aksoy, Başak; Sezgin, Gülay; Albayrak, Davut; Sezgin Evim, Melike; Zengin, Emine; Pekpak, Esra; Turkish Pediatric Bone Marrow Transplantation Study Group
    Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most frequent cause ofpost-transplantation mortality. Isolated extramedullary (EM) relapse (iEMR) after HSCT is relatively rare and notwell characterized, particularly in pediatric patients. We retrospectively analyzed 1527 consecutive pediatricpatients with acute leukemia after allo-HSCT to study the incidence, risk factors, and outcome of iEMR comparedwith systemic relapse. The 5-year cumulative incidence of systemic relapse (either bone marrow [BM] only or BMcombined with EMR) was 24.8%, and that of iEMR was 5.5%. The onset of relapse after allo-HSCT was significantlylonger in EM sites than in BM sites (7.19 and 5.58 months, respectively;P= .013). Complete response (CR) 2+/active disease at transplantation (hazard ratio [HR], 3.1;P<.001) and prior EM disease (HR, 2.3;P= .007) were independent risk factors for iEMR. Chronic graft-versus-host disease reduced the risk of systemic relapse (HR, 0.5;P= .043) but did not protect against iEMR. The prognosis of patients who developed iEMR remained poor but wasslightly better than that of patients who developed systemic relapse (3-year overall survival, 16.5% versus 15.3%;P= .089). Patients experiencing theirfirst systemic relapse continued to have further systemic relapse, but only aminority progressed to iEMR, whereas those experiencing their iEMR atfirst relapse developed further systemicrelapse and iEMR at approximately similar frequencies. A second iEMR was more common after afirst iEMR thanafter afirst systemic relapse (58.8% versus 13.0%;P= .001) and was associated with poor outcome. iEMR has apoor prognosis, particularly after a second relapse, and effective strategies are needed to improve outcomes.© 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
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    Extracorporeal photopheresis did not prevent the development of an autoimmune disease: Myasthenia gravis
    (Wiley-Blackwell, 2016) Uygun, Vedat; Daloğlu, Hayriye; Öztürkmen, Seda Irmak; Döşemeci, Levent; Karasu, Gülsün; Hazar, Volkan; Yeşilipek, Akif
    BACKGROUNDMyasthenia gravis (MG) is a neuromuscular disorder characterized by an autoimmune defect in the neuromuscular junction. In most patients, the autoimmune attack is mediated by antibodies against the acetylcholine receptor (AChR) on the postsynaptic membrane. Deficient immunoregulation, including regulatory T cells, is consistently observed. Extracorporeal photopheresis (ECP) leads to the induction of regulatory T cells that mediate immunologic tolerance in autoimmune diseases; however, the data regarding MG are very limited. CASE REPORTHere, we report a patient who, during ongoing ECP therapy for his severe, refractory, chronic graft-versus-host disease (cGVHD), developed MG, although he responded very well to ECP, as indicated by the lowering of his chronic cGVHD severity grade to moderate. RESULTSDespite receiving ECP, our patient developed MG, which was resistant to treatment and required intensive care unit support. CONCLUSIONSClose surveillance is required when ECP is planned as one of the treatment alternatives in myasthenia gravis that develop in cGVHD.
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    Prognostic factors for survival in children who relapsed after allogeneic hematopoietic stem cell transplantation for acute leukemia
    (Wiley, 2021) Hazar, Volkan; Tezcan Karasu, Gülsün; Öztürk, Gülyüz; Küpesiz, Alphan; Aksoylar, Serap; Özbek, Namık; Gökçe, Müge; Fışgın, Tunç
    Background 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.
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    Thalassemia-free and graft-versus-host-free survival: Outcomes of hematopoietic stem cell transplantation for thalassemia major, Turkish experience
    (Bone Marrow Transplantation, 2022) Yeşilipek, M. Akif; Uygun, Vedat; Küpesiz, Alphan; Karasu, Gülsün; Öztürk, Gülyüz; Ertem, Mehmet; Şaşmaz, İlgen; Daloğlu, Hayriye; Güler, Elif; Hazar, Volkan; Fışgın, Tunç; Sezgin, Gülay; Kansoy, Savaş; Kuşkonmaz, Barış; Akıncı, Burcu; Özbek, Namık; Ünal-İnce, Elif; Öztürkmen, Seda; Küpesiz-Tayfun, Funda; Yalçın, Koray; Anak, Sema; Bozkurt, Ceyhun; Karakükçü, Musa; Küpeli, Serhan; Albayrak, Davut; Öniz, Haldun; Aksoylar, Serap; Visal-Okur, Fatma; Albayrak, Canan; Demir-Yenigürbüz, Fatma; Ok-Bozkaya, İkbal; İleri, Talia; Gürsel, Orhan; Karagün, Barbaros Şahin; Tüysüz-Kintrup, Gülen; Çelen, Suna; Elli, Murat; Adaklı-Aksoy, Başak; Yılmaz, Ebru; Tanyeli, Atila; Turan-Akyol, Şule; Önder-Siviş, Zuhal; Özek, Gülcihan; Uçkan, Duygu; Kartal, İbrahim; Atay, Didem; Arzu, Akyay; Arman-Bilir, Özlem; Çakmaklı, Hasan Fatih; Kürekçi, Emin; Malbora, Barış; Akbayram, Sinan; Demir, Hacı Ahmet; Kılıç, Suar Çakı; Güneş, Adalet Meral; Zengin, Emine; Özmen, Salih; Antmen, Ali Bülent
    We report the national data on the outcomes of hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) patients in Turkey on behalf of the Turkish Pediatric Stem Cell Transplantation Group. We retrospectively enrolled 1469 patients with TM who underwent their first HSCT between 1988 and 2020 in 25 pediatric centers in Turkey. The median follow-up duration and transplant ages were 62 months and 7 years, respectively; 113 patients had chronic graft versus host disease (cGVHD) and the cGVHD rate was 8.3% in surviving patients. Upon the last visit, 30 patients still had cGvHD (2.2%). The 5-year overall survival (OS), thalassemia-free survival (TFS) and thalassemia-GVHD-free survival (TGFS) rates were 92.3%, 82.1%, and 80.8%, respectively. cGVHD incidence was significantly lower in the mixed chimerism (MC) group compared to the complete chimerism (CC) group (p < 0.001). In survival analysis, OS, TFS, and TGFS rates were significantly higher for transplants after 2010. TFS and TGFS rates were better for patients under 7 years and at centers that had performed over 100 thalassemia transplants. Transplants from matched unrelated donors had significantly higher TFS rates. We recommend HSCT before 7 years old in thalassemia patients who have a matched donor for improved outcomes.