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    Comparison of outcomes of total body irradiation (TBI) vs non-TBI conditioning regimens in acute lymphoblastic leukemia for allogeneic transplantation
    (Nature Publishing Group, 2019) Beköz, Hüseyin Saffet; Sevindik, Ömür Gökmen; Özçelik, Tülay; Arat, Mutlu; Hindilerden, İpek Yonal; Beşışık, Sevgi Kalayoğlu; Nalcacı, Meliha; Uzay, Ant; Kartı, Süleyman Sami; Kıvanç, Demet; Sargın, Deniz
    [Abstract Not Available]
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    Current practice of autologous hematopoietic progenitor cell mobilization in adult patients with multiple myeloma and lymphoma: The results of a survey from Turkish hematology research and education group (ThREG)
    (Pergamon-Elsevier Science Ltd., 2017) Tekgündüz, Emre; Demirkan, Fatih; Vural, Filiz; Göker, Hakan; Özdoğu, Hakan; Kiki, İlhami; Aydoğdu, İsmet; Kaynar, Leylagül; Erkurt, Mehmet Ali; Çağırgan, Seçkin; Beşışık, Sevgi; Dağdaş, Simten; Koca, Ebru; Kadıköylü, Gürhan; Gündüz, Eren; Yılmaz, Mehmet; Beköz, Hüseyin; Ural, Ali Uğur; Baştürk, Abdulkadir; Arat, Mutlu; Albayrak, Murat; Öztürk, Erman; Akyol, Alev; Bolaman, Ali Zahit; Nevruz, Oral; Özkan, Hasan Atilla; Özgür, Gökhan; Altuntaş, Fevzi
    Autologous hematopoietic cell transplantation (AHCT) is an established treatment option for adult patients presenting with multiple myeloma (MM), Hodgkin lymphoma (HL) and various subtypes of non-Hodgkin lymphoma (NHL) in upfront and/or relapsed/refractory disease settings. Although there are recently published consensus guidelines addressing critical issues regarding autologous hematopoietic progenitor cell mobilization (HPCM), mobilization strategies of transplant centers show high variability in terms of routine practice. In order to understand the current institutional policies regarding HPCM in Turkey and to obtain the required basic data for preparation of a national positional statement on this issue, Turkish Hematology Research and Education Group (ThREG) conducted a web-based HPCM survey. The survey was designed to include multiple-choice questions regarding institutional practice of HPCM in adults presenting MM, HL, and NHL. The representatives of 27 adult HCT centers participated to the study. Here we report the results of this survey shedding light on the real world experience in Turkey in terms of autologous HPCM mobilization strategies in patients presenting with MM and lymphoma. (C) 2017 Elsevier Ltd. All rights reserved.
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    HLA-A allele mismatch (7/8 or 9/10) is the second best option after 8/8 or 10/10 matched unrelated donors: An analysis on results from Turkish centers
    (Nature Publishing Group, 2015) Beksaç, Meral; Savran Oğuz, Fatma; Topçuoğlu, Pervin; Karasu, Gülsun; Arat, Mutlu; Aksoylar, Serap; Kansoy, Savaş; Kalayoğlu Beşışık, Sevgi; Küpesiz, Alphan; Hazar, Volkan; Altuntaş, Fevzi; Ünal, Ali; Gülbaş, Zafer; Sargın, Fatma Deniz; İlhan, Osman; Gürman, Günhan; Yeşilipek, Akif
    Introduction: Hematopoietic stem cell transplantation (HSCT) from an unrelated donor has been established as an effective treatment option for patients with hematological diseases who lack a human leukocyte antigen (HLA)-matched related donor. However, HLA mismatch at the genetic level (allele mismatch) may be observed among serologically HLAmatched (antigen match) donor-recipient pairs, which adversely affects the incidence of severe graft-versus-host disease (GVHD) and survival. The aim of this retrospective multicenter study was to evaluate the impact of HLA mismatch on unrelated transplantation outcomes in Turkey. Materials (or patients) and methods: The data set consisted of follow-up records of 444 (of which 436 with HLA matching data available) unrelated-donor stem cell transplantations performed at 14 centers between July 2002- September 2014 and facilitated by TRAN orTRIS .215 patients underwent single antigen and/or allele-mismatched (mm) HSCT. The distribution of the mismatches according to the HLA-A, HLA-B, HLA-C, and HLA-DR and HLA-DQ loci are:82, 58, 32, 35 and 9 patients, respectively.Twelve patients were transplanted with 8/10 HLA matching. The patients’ characteristics are summarized in Table 1. Results: The neutrophil engraftment was achieved in 82.2% of the patients. HLA mm has a negative impact on engraftment (HLA mm: median 17days vs HLA-matched: median 16 days, p=0.03). Acute GVHD wasobserved at a rate of 42.1%. HLA matching did not have an impact on the incidence of acute GvHD (p=0.35) but chronic GvHD was more frequent among HLA allele /antigen mismatched patients than HLA-matched (p=0.008). The possibility of 5-year overall survival (OS) was 50.2%±2.5%. The presence of HLA mismatch significantly shortened the OS (58.9±3.4% vs Allele mm: 49.8±5.7% vs Antigen mm 36.0±4.9%, p<0.0001).Among the allele level mm HLA-A mm was associated with better OS compared to other loci (55.9±11.7%vs. 17.2±8.2%). When analysis was performed regardless of HLA match or only among HLA matched donor-recipient-pairsgender and stem cell source (PB vs BM) did not have an impact on OS. The OS of patients transplanted between 2002-2007 were shorter than those transplanted later (2008-2014)(37.9±6.4% vs. 52.9±2.7; p= 0.02).
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    Nivolumab for relapsed or refractory hodgkin lymphoma experience in Turkey
    (Ferrata Storti Foundation, 2017) Ferhanoğlu, Burhan; Beköz, Hüseyin Saffet; Karadurmuş, Nuri; Paydaş, Semra; Gülbaş, Zafer; Türker, Alev; Toptaş, Tayfur; Fıratlı Tuğlular, Tülin; Tekgündüz, Emre; Kaya, Ali Hakan; Taştemir, N.; Arat, Mutlu; Pepedil Tanrıkulu, Funda; Özkocaman, Vildan; Abalı, Hüseyin; Turgut, Mehmet; Kaynar, Leylagül; Karadoğan, İhsan; Özbalak, Murat; Özcan, Muhit; Doğu, Mehmet Hilmi; Kabukçu Hacıoğlu, Sibel; Yıldırım, Rahsan; Barışta, İbrahim; Demirkaya, Metin; Köseoğlu, Fatoş Dilan; Yüksel, Meltem Kurt; Sönmez, Mehmet; Toprak, Selami Koçak
    [Abstract Not Available]
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    Nivolumab for relapsed or refractory Hodgkin lymphoma: Real-life experience
    (Springer, 2020) Beköz, Hüseyin; Özbalak, Murat; Karadurmuş, Nuri; Paydaş, Semra; Türker, Alev; Toptaş, Tayfur; Fıratlı Tuğlular, Tülin; Altuntaş, Fevzi; Kızıl Çakar, Merih; Sönmez, Mehmet; Gülbaş, Zafer; Demir, Nazlı; Kaynar, Leylagül; Yıldırım, Rahşan; Karadoğan, İhsan; Arat, Mutlu; Kapucu, İrem; Alayvaz Aslan, Nevin; Özkocaman, Vildan; Turgut, Mehmet; Kurt Yüksel, Meltem; Özcan, Muhit; Kabukçu Hacıoğlu, Sibel; Barışta, İbrahim; Demirkaya, Metin; Saydam, Güray; Toprak, Selami Koçak; Yılmaz, Mehmet; Demirkol, Onur; Ferhanoğlu, Burhan
    Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, in approximately one-third of the responding patients, the disease relapses following completion of therapy. One of the drugs that have been approved for the treatment of relapsed/refractory cHL is nivolumab, an immune check point inhibitor that shows its effects by blocking the programmed death 1 (PD-1) receptor. In this study, we present a retrospective "real-life" analysis of the usage of nivolumab in patients with relapsed/refractory cHL that have joined the named patient program (NPP) for nivolumab, reflecting 4 years of experience in the treatment of relapsed/refractory cHL. We present a retrospective analysis of 87 patients (median age, 30) that participated in the NPP in 24 different centers, who had relapsed/refractory cHL and were consequently treated with nivolumab. The median follow-up was 29 months, and the median number of previous treatments was 5 (2-11). In this study, the best overall response rate was 70% (CR, 36%; PR, 34%). Twenty-eight of the responding patients underwent subsequent stem cell transplantation (SCT). Among 15 patients receiving allogeneic stem cell transplantation, 9 patients underwent transplantation with objective response, of which 8 of them are currently alive with ongoing response. At the time of analysis, 23 patients remained on nivolumab treatment and the rest discontinued therapy. The main reason for discontinuing nivolumab was disease progression (n = 23). The safety profile was acceptable, with only nine patients requiring cessation of nivolumab due to serious adverse events. The 24-month progression-free and overall survival rates were 58.5% (95% CI, 0.47-0.68) and 78.7% (95% CI, 0.68-0.86), respectively. Eighteen patients died during the follow-up and only one of these was regarded to be treatment-related. With its efficacy and its safety profile, PD-1 blockers became an important treatment option in the heavily pretreated cHL patients.
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    Preliminary report of the academic CAR-T (ISIKOK-19) cell clinical trial in Turkey: Characterization of product and outcomes of clinical application
    (Turkish Society of Hematology, 2022) Erdoğan, Ebru; Yalçın, Koray; Hemşinlioğlu, Cansu; Sezgin, Aslıhan; Seyis, Utku; Kançağı, Derya Dilek; Taştan, Cihan; Yurtsever, Bulut; Turan, Raife Dilek; Çakırsoy, Didem; Abanuz, Selen; Sır Karakuş, Gözde; Elek, Muhammer; Beköz, Hüseyin Saffet; Gemici, Aliihsan; Sargın, Deniz; Arat, Mutlu; Ferhanoğlu, Burhan; Pekgüç, Ebru; Örnek, Serdar; Büyüktaş, Deram; Birgen, Nur; Ratip, Siret; Ovalı, Ercüment
    Objective: Chimeric antigen receptor T (CAR-T) cell therapies have already made an impact on the treatment of B-cell malignancies. Although CAR-T cell therapies are promising, there are concerns about commercial products regarding their affordability and sustainability. In this preliminary study, the results of the first production and clinical data of an academic CAR-T cell (ISIKOK-19) trial in Turkey are presented. Materials and Methods: A pilot clinical trial (NCT04206943) designed to assess the safety and feasibility of ISIKOK-19 T-cell therapy for patients with relapsed and refractory CD19+ tumors was conducted and participating patients received ISIKOK-19 infusions between October 2019 and July 2021. The production data of the first 8 patients and the clinical outcome of 7 patients who received ISIKOK-19 cell infusions are presented in this study. Results: Nine patients were enrolled in the trial [5 with acute lymphoblastic leukemia (ALL) and 4 with non-Hodgkin lymphoma (NHL)], but only 7 patients could receive treatment. Two of the 3 participating ALL patients and 3 of the 4 NHL patients had complete/ partial response (overall response rate: 72%). Four patients (57%) had CAR-T-related toxicities (cytokine release syndrome, CAR-T-related encephalopathy syndrome, and pancytopenia). Two patients were unresponsive and had progressive disease following CAR-T therapy. Two patients with partial response had progressive disease during follow-up. Conclusion: Production efficacy and fulfillment of the criteria of quality control were satisfactory for academic production. Response rates and toxicity profiles were also acceptable for this heavily pretreated/refractory patient group. ISIKOK-19 cells appear to be a safe, economical, and efficient treatment option for CD19+ tumors. However, the findings of this study need to be supported by the currently ongoing ISIKOK-19 clinical trial.