Browsing by Author "Beksaç, Meral"

Now showing 1 - 11 of 11
  • No Thumbnail Available
    Item
    A real world multicenter retrospective study on extramedullary disease from Balkan Myeloma Study Group and Barcelona University: Analysis of parameters that improve outcome
    (2020) Beksaç, Meral; Seval, Güldane Cengiz; Dil ve Tarih-Coğrafya Fakültesi
    Here, we report the outcome of 226 myeloma patients presenting with extramedullary plasmacytoma or paraosseous involvement in a retrospective study conducted in 19 centers from 11 countries. Extramedullary disease was detected at diagnosis or relapse between January 2010 and November 2017. Extramedullary plasmacytoma and paraosseous involvement were observed in 130 patients at diagnosis (92 of 38) and in 96 at relapse (84 of 12). The median time from multiple myeloma diagnosis to the development of extramedullary disease was 25.1 months (range 3.1-106.3 months) in the relapse group (median follow up: 15 months). Imaging approach for extramedullary disease was computed tomography (n=133), positron emission tomography combined with computed tomography (n=50), or magnetic resonance imaging (n=35). The entire group received a median two lines of treatment and autologous stem cell transplantation (44%) following the diagnosis of extramedullary disease. Complete response was higher for paraosseous involvement versus extramedullary plasmacytoma at diagnosis (34.2% vs. 19.3%; P=NS.) and relapse (54.5% vs. 9%; P=0.001). Also paraosseous involvement patients had a better progression-free survival (PFS) when recognized at initial diagnosis of myeloma than at relapse (51.7 vs. 38.9 months). In addition, overall survival was better for paraosseous involvement compared to extramedullary plasmacytoma at diagnosis (not reached vs. 46.5 months). Extramedullary plasmacytoma at relapse had the worst prognosis with a PFS of 13.6 months and overall survival of 11.4 months. In the multivariate analysis, paraosseous involvement, extramedullary disease at diagnosis, International Staging System (ISS-I), and undergoing autologous stem cell transplantation improved overall survival independently. This cohort demonstrated that extramedullary disease benefits from front-line autologous stem cell transplantation and extramedullary plasmacytoma differs from paraosseous involvement in terms of rate and duration of response, with even worse outcomes when detected at relapse, constituting an unmet clinical need. © 2020 Ferrata Storti Foundation
  • No Thumbnail Available
    Item
    Ankara Üniversitesi Kordon Kanı ve Kök Hücre Bankası: hizmet ve alt yapı devamlılığı projesi
    (Ankara Üniversitesi Bilimsel Araştırma Projeleri, 2015) Beksaç, Meral; Tıp Fakültesi; İlhan,Osman; Dalva,Clara
    Bu proje ile Devlet Planlama Teşkilatı “AÜ Kordon Kanı, Kan ve Kök Hücre Bankası” adlı 2009 da kamu alt yapı projesi kapsamında kurulan AÜTF Akraba Dışı Doku Bankası-Gönüllü Verici merkezi ile Kordon Kanı Bankası hizmet ve faaliyetlerinin devam edebilmesi, gereksinimlerinin karşılanması hedeflenmiştir. DPT desteği öncesi mevcut koşullarda başlatılan bu yapılanma önce DPT daha sonra BAP proje kapsamında uluslararası standartların gerektirdiği koşullara kavuşarak kordon kanı bankacılığı için gerekli olan Good Manufacturing Practice (GMP) ile uyumlu alt yapısını oluşturmuştur. 8-9.02.2011 tarihinde İl Sağlık Müdürlüğü ve Sağlık Bakanlığı Teftiş Kurulu GMP müfettişleri tarafından yerinde denetlenerek Sağlık Bakanlığı Tedavi Hizmetler Genel Müdürlüğünde Ulusal Kordon Kanı Kurulunun değerlendirmesi sonucunda 13/07/2011 da ruhsata uygun bulunmuştur.. DPT projesi ile 2010 yılı sonuna kadar sarf malzemelerinin çoğu, Eylül 2011 e kadar yetecek sıvı azot takviyesi, 2011 yılı Ekim sonuna kadar 5 elemanın maaşları karşılanmış olan kordon kanı bankasının devamlılığı için sarf ve eleman temini amacıyla mali destek gerekli olduğu için bu proje verilmiştir. Projenin hedefi Ankara Üniversitesi Tıp Fakültesi kapsamındaki gönüllü vericilerin ve bağışlanan kordon kanı sayısını en az 20 000 e yükseltmek; ayrıca kurulan akraba dışı doku bankasının WMDA, kordon kanı bankasının FACT/NETCORD tarafından akreditasyonu olarak hedeflenmiştir. Bu proje bitiminde akraba dışı gönüllü verici sayımız 30.178, doku tiplendirmesi yapılmış olan 13.061 vericiye, 1035 kordon kanına ulaşılmıştır. Bu vericilerden 18 kök hücre nakli ve ilaveten 4 ü akraba dışı toplam 16 kordon kanı nakli gerçekleştirilmiştir. Bu proje ile Türkiye’de ilk kez kamuda oluşan bu yapılanma ülkemiz için yurtdışına döviz kaybını azaltmış ve azaltmaya da devam etmektedir. İlaveten uluslararası akreditasyon yönündeki faaliyetlerimiz son aşamaya gelmiştir. Proje hedeflerini aşarak Türkiye’de öncül rolünü devam ettirmektedir.
  • No Thumbnail Available
    Item
    Çeşitli hematopoietik dokularda mezankimal kök hücrelerin nicel olarak gösterilmesi
    (Sağlık Bilimleri Enstitüsü, 2007) Ersoy, Hakan; Beksaç, Meral; İç Hastalıkları
    Mesenchymal Stem Cells (MSCs) are important because of having the ability to differentiate different cell and tissue types. Although specific monoclonal antibodies defining MSCs have been developed, there are no standardized methods to measure the density of MSCs in samples by flow cytometry and immunohistochemical methods. The aim of this study is to determine the best antibody to be used in density measurement studies of MSCs found in samples by flow cytometry and immunohistochemical methods. Umbilical cord blood (n:15), stimulated peripheric blood (n:8), culture of MSC (n:6), adult bone marrow (n:8), pediatric bone marrow (n:2) and the section of umbilical cords (n:13) was evaluated by flow cytometry and immunohistochemical methods. In subamniotic area MSC availability was observed. The used MSC specific MoAb?s are: CD29, CD45, Stro-1, HLA-DR, CD73, CD34, CD90, CD105 and CD44. The findings that prove the MSC existence are negative reactions of CD45 and positive reactions of CD90, CD105, CD73, and CD29. After the study, the highest affinities in the flow cytometry were for CD105, CD29, CD90 and CD105. MSC specific Stro-1 and CD44 antibodies were observed in perivascular area densely. Stro-1 and CD44 antibodies were used in immunohistochemical study of umbilical cord blood samples. No MSC existence was observed in sub amniotic area. Not observing mesoderm sourced MSC is accepted as normal in this area. MSC specific Stro-1 and CD44 antibodies were observed in perivascular area densely. Similarly, mesoderm based MSCs were observed rarely in intervascular area. The maximum amount of MSCs in bone marrow was found in the rate of 0,69%, in stimulated peripheric blood was found in the rate of 0,085% and the lowest MSCs concentration was observed in Umbilical Cord Blood as 0,025%. As a result, bone marrow was found as the best MSC resource.
  • No Thumbnail Available
    Item
    Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR
    (2018) Beksaç, Meral; Tıp fakültesi
    Daratumumab, a CD38 human monoclonal antibody, demonstrated significant clinical activity in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in the primary analysis of CASTOR, a phase 3 study in relapsed and/or refractory multiple myeloma. A post hoc analysis based on treatment history and longer follow up is presented. After 19.4 (range: 0-27.7) months of median follow up, daratumumab plus bortezomib and dexamethasone prolonged progression-free survival (median: 16.7 versus 7.1 months; hazard ratio, 0.31; 95% confidence interval, 0.24-0.39; P P12, ≤6, or >6 months), or cytogenetic risk. Minimal residual disease–negative rates were >2.5-fold higher with daratumumab across subgroups. The safety profile of daratumumab plus bortezomib and dexamethasone remained consistent with longer follow up. Daratumumab plus bortezomib and dexamethasone demonstrated significant clinical activity across clinically relevant subgroups and provided the greatest benefit to patients treated at first relapse. Trial registration: clinicaltrials.gov identifier: 02136134.
  • No Thumbnail Available
    Item
    Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR
    (2018) Beksaç, Meral; Tıp Fakültesi
    Daratumumab, a CD38 human monoclonal antibody, demonstrated significant clinical activity in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in the primary analysis of CASTOR, a phase 3 study in relapsed and/or refractory multiple myeloma. A post hoc analysis based on treatment history and longer follow up is presented. After 19.4 (range: 0-27.7) months of median follow up, daratumumab plus bortezomib and dexamethasone prolonged progression-free survival (median: 16.7 versus 7.1 months; ha zard ra ti o, 0.3 1; 95% confidence interval, 0.24 -0.39; P<0.0001) and improved the overall response rate (83.8% versus 63.2%; P<0.0001) compared with bortezomib and dexamethasone alone. The progression-free survival benefit of daratumumab plus bortezomib and dexamethasone was most apparent in patients with 1 prior line of therapy (median: not reached versus 7.9 months; hazard ratio, 0.19; 95% confidence interval, 0.12-0.29; P<0.0001). Daratumumab plus bortezomib and dexamethasone was also superior to bortezomib and dexamethasone alone in subgroups based on prior treatment exposure (bortezomib, thalidomide, or lenalidomide), lenalidomide-refractory status, time since last therapy (≤12, >12, ≤6, or >6 months), or cytogenetic risk. Minimal residual disease–negative rates were >2.5-fold higher with daratumumab across subgroups. The safety profile of daratumumab plus bortezomib and dexamethasone remained consistent with longer follow up. Daratumumab plus bortezomib and dexamethasone demonstrated significant clinical activity across clinically relevant subgroups and provided the greatest benefit to patients treated at first relapse. © 2018 Ferrata Storti Foundation.
  • No Thumbnail Available
    Item
    European myeloma network guidelines for the management of multiple myeloma-related complications
    (2015) Beksaç, Meral; Fen Fakültesi
    The European Myeloma Network provides recommendations for the management of the most common complications of multiple myeloma. Whole body low-dose computed tomography is more sensitive than conventional radiography in depicting osteolytic disease and thus we recommend it as the novel standard for the detection of lytic lesions in myeloma (grade 1A). Myeloma patients with adequate renal function and bone disease at diagnosis should be treated with zoledronic acid or pamidronate (grade 1A). Symptomatic patients without lytic lesions on conventional radiography can be treated with zoledronic acid (grade 1B), but its advantage is not clear for patients with no bone involvement on computed tomography or magnetic resonance imaging. In asymptomatic myeloma, bisphosphonates are not recommended (grade 1A). Zoledronic acid should be given continuously, but it is not clear if patients who achieve at least a very good partial response benefit from its continuous use (grade 1B). Treatment with erythropoietic-stimulating agents may be initiated in patients with persistent symptomatic anemia (hemoglobin <10g/dL) in whom other causes of anemia have been excluded (grade 1B). Erythropoietic agents should be stopped after 6-8 weeks if no adequate hemoglobin response is achieved. For renal impairment, bortezomib-based regimens are the current standard of care (grade 1A). For the management of treatment-induced peripheral neuropathy, drug modification is needed (grade 1C). Vaccination against influenza is recommended; vaccination against streptococcus pneumonia and hemophilus influenza is appropriate, but efficacy is not guaranteed due to suboptimal immune response (grade 1C). Prophylactic aciclovir (or valacyclovir) is recommended for patients receiving proteasome inhibitors, autologous or allogeneic transplantation (grade 1A). © 2015 Ferrata Storti Foundation.
  • No Thumbnail Available
    Item
    Ex Vivo granülositer koloni oluşturan insan göbek kordon kanı hücrelerinin kök hücre fenotip analizi
    (Biyoteknoloji Enstitüsü, 2014) Gençer, Emine Begüm; Beksaç, Meral; Other
  • No Thumbnail Available
    Item
    Fatal fulminant hepatic failure during treatment of multiple myeloma
    (2005) Ertek, Sibel; Arat, Mutlu; Soykan, İrfan; İdilman, Ramazan; Ekinci, Cemil; Beksaç, Meral
  • No Thumbnail Available
    Item
    Impact of "killer immunoglobulin-like receptor/ligand" genotypes on outcome following surgery among patients with colorectal cancer: activating KIRS are associated with long-term disease free survival
    (2015) Dalva, Klara; Beksaç, Meral; Kök Hücre Enstitüsü; Tıp Fakültesi
    Approximately 30% of patients with stage II/III colorectal cancer develop recurrence following surgery. How individual regulation of host mediated anti-tumor cytotoxicity is modified by the killer-cell immunoglobulin-like receptor (KIRs) genotype is essential for prediction of outcome. We analyzed the frequency of KIR and KIR ligand Human Leukocyte Antigen Class I genotypes, and their effects on recurrence and disease-free survival (DFS). Out of randomly selected 87 colorectal cancer patients who underwent R0 resection operations between 2005 and 2008, 29 patients whose cancers progressed within a median five-year follow-up period were compared with 58 patients with no recurrence within the same time period. Recurrent cases shared similar tumor stages with non-recurrent cases, but had different localizations. We used DNA isolated from pathological archival lymphoid and tumor tissues for KIR and KIR ligand (HLA-C, group C1, group C2, and HLA-A-Bw4) genotyping. Among cases with recurrence, KIR2DL1 (inhibitory KIR) and A-Bw4 (ligand for inhibitory KIR3DL1) were observed more frequently (p=0.017 and p=0.024); and KIR2DS2 and KIR2DS3 (both activating KIRs) were observed less frequently (p=0.005 and p=0.043). Similarly, in the non-recurrent group, inhibitory KIR-ligand combinations 2DL1-C2 and 2DL3-C1 were less frequent, while the activating combination 2DS2-C1 was more frequent. The lack of KIR2DL1, 2DL1-C2, and 2DL3-C1 improved disease-free survival (DFS) (100% vs. 62.3%, p=0.05; 93.8% vs. 60.0%, p=0.035; 73.6% vs. 55.9%, p=0.07). The presence of KIR2DS2, 2DS3, and 2DS2-C1 improved DFS (77.8% vs. 48.5%, p=0.01; 79.4% vs. 58.5%, p=0.003; 76.9% vs. 51.4%, p=0.023). KIR2DS3 reduced the risk of recurrence (HR=0.263, 95% CI =0.080-0.863, p=0.028). The number of activating KIRs are correlated strongly with DFS, none/one/two KIR : 54/77/98 months (p=0.004). In conclusion the inheritance of increasing numbers of activating KIRs and lack of inhibitory KIRs, independent of tumor localization or stage, is associated with long-term DFS.
  • No Thumbnail Available
    Item
    Impact of“Killer Immunoglobulin-LikeReceptor /Ligand”Genotypes on Outcomefollowing Surgery among Patients withColorectal Cancer: Activating KIRs AreAssociated with Long-Term Disease FreeSurvival
    (2015) Beksaç, Meral; Dalva, Klara; Tıp Fakültesi
    Approximately 30%of patients with stage II/III colorectal cancer develop recurrence following surgery. How individual regulation of host mediated anti-tumor cytotoxicity is modified by the killer-cell immunoglobulin-like receptor (KIRs) genotype is essential for prediction of outcome. We analyzed the frequency of KIR and KIR ligand Human Leukocyte Antigen Class I genotypes, and their effects on recurrence and disease-free survival (DFS). Out of randomly selected 87 colorectal cancer patients who underwent R0 resection operations between 2005 and 2008, 29 patients whose cancers progressed within a median five-year follow-up period were compared with 58 patients with no recurrence within the same time period. Recurrent cases shared similar tumor stages with non-recurrent cases, but had different localizations.We used DNA isolated from pathological archival lymphoid and tumor tissues for KIR and KIR ligand (HLA-C, group C1, group C2, and HLA-A-Bw4) genotyping. Among cases with recurrence, KIR2DL1 (inhibitory KIR) and A-Bw4 (ligand for inhibitory KIR3DL1) were observed more frequently (p=0.017 and p=0.024); and KIR2DS2 and KIR2DS3 (both activating KIRs) were observed less frequently (p=0.005 and p=0.043). Similarly, in the non-recurrent group, inhibitory KIR-ligand combinations 2DL1-C2 and 2DL3-C1 were less frequent, while the activating combination 2DS2-C1 was more frequent. The lack of KIR2DL1, 2DL1-C2, and 2DL3-C1 improved disease-free survival (DFS) (100% vs. 62.3%, p=0.05; 93.8% vs. 60.0%, p=0.035; 73.6% vs. 55.9%, p=0.07). The presence of KIR2DS2, 2DS3, and 2DS2-C1 improved DFS (77.8% vs. 48.5%, p=0.01; 79.4% vs. 58.5%, p=0.003; 76.9% vs. 51.4%, p=0.023). KIR2DS3 reduced the risk of recurrence (HR=0.263, 95% CI = 0.080-0.863, p=0.028). The number of activating KIRs are correlated strongly with DFS, none/ one/ two KIR: 54/77/98 months (p=0.004). In conclusion the inheritance of increasing numbers of activating KIRs and lack of inhibitory KIRs, independent of tumor localization or stage, is associated with long-term DFS.
  • No Thumbnail Available
    Item
    Kordon kanı, maternal plazma ve amniyon sıvısındaki sitokin seviyelerinin serolojik yöntemlerle belirlenmesi ve kordon kanı in vitro koloni oluşturma potansiyeline etkisi
    (Biyoteknoloji Enstitüsü, 2017) Akın, Hasan Yalım; Beksaç, Meral; Biyoteknoloji
    İnsan hematopoietik kök hücrelerinin (HKH) proliferasyonu ve farklılaşması sitokinler ile düzenlenir. Başlıca kemik iliği (Kİ), çevre kanı (PK) ve göbek kordon kanı (KK) kaynaklı HKH naklinde kısa dönemli yapılanma sağlayan CD34+ HKH'lerin engrafman kapasitelerinin in vitro belirlenmesinde kullanılan en yaygın yöntem koloni oluşturma (CFU) testleridir. CFU testleri, ortama eklenen çeşitli hematopoietik sitokinler aracılığıyla HKH'lerin proliferasyon ve farklılaşma potansiyellerinin belirlenmesi amacıyla Kİ koşullarının yarı-katı besiyerinde taklit edilmesi temeline dayanır. Günümüzde bu amaçla en yaygın kullanılan sitokinler, tarihsel olarak önceleri amniyon sıvısı (AS) veya hücre serisi kaynaklı iken daha sonra rekombinant insan proteinleri kullanıma girmiştir. Hassas ve optimal konsantrasyonlarda kullanılabilmeleri yönünden avantajlı olan bu proteinlerin çok düşük miktarlarının pahalı olması ve saklama koşullarının zorluğu gibi dezavantajları nedeniyle farklı sitokin kaynakları arayışına gidilmektedir. Günümüzde kullanılmayan, elde edilmesi kolay, doğal, otolog sitokin kaynakları bu soruna çözüm oluşturabilir. Gebelik sürecinde fetal gelişim sürecinde hematopoietik sitokin düzeylerinde artış, maternal çevre kanında (MK) ve KK'da Granülosit-Koloni Stimüle Edici Faktör (G-CSF) düzeylerinin belirlenmesine yönelik kısıtlı sayıda araştırmada gösterilmiştir. Bu verilerden yola çıkarak, bu tez çalışmasında MK, KK ve AS'nin in vitro KK kısa dönem CFU potansiyeline etkisi ve bu kaynaklardaki hematopoezde kritik rol oynayan Kök Hücre Faktörü (SCF), G-CSF ve İnterlökin (IL)-3 sitokin düzeylerinin direkt Enzyme-Linked Immunosorbent Assay (ELISA) yöntemi ile belirlenmesi hedeflenmiştir. Araştırmaya 20 elektif sezaryen olgu dahil edilmiştir. MK ve KK plazmaları ve AS ile desteklenen erken dönem CFU testlerinde koloni oluşturulamamıştır. Öte yandan, AS ve KK plazmasında sırasıyla G-CSF (1.068 pg/ml; aralık: 613-3.996) ve SCF (1.761 pg/ml; aralık: 1.089-2.514) konsantrasyonları yüksek düzeylerde saptanmıştır. Yüksek düzeyde SCF içeren KK plazması, in vitro agar kolonizasyonunda olmasa bile sıvı kültürde HKH ekspansiyonunda destekleyici bir bileşen olarak proliferasyon hızının arttırılmasına katkı sağlayabilir. Bulgularımız ışığında HKH nakillerinde yaygın olarak kullanılan plazma ve eritrosit uzaklaştırılmış KK yerine plazma içeren ürününün kullanılması engrafman başarısına katkı sağlama olasılığı taşımaktadır.