Person: TOPTAŞ, TAYFUR
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TOPTAŞ
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TAYFUR
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Publication Open Access Predictive immune markers for disease progression in multiple myeloma and monoclonal gammopathy of undetermined significance(2022-12-01) TOPTAŞ, TAYFUR; TÜRKÖZ, HÜSEYİN KEMAL; İşgör İ. Ş., TOPTAŞ T., TÜRKÖZ H. K.©Copyright 2022 by Turkish Society of Hematology | Turkish Journal of Hematology, Published by Galenos Publishing HouseObjective: Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM, are plasma cell neoplasms. The evolution of the treatment of MM in recent years has dramatically improved the outcome for these patients. Currently, multidisciplinary studies are being conducted to elucidate the etiopathogenesis of the disease and develop specific treatment agents and prognostic markers. The present study investigates the relationships between immunoexpression of CD138, Pan-Ras, CCL-3, DKK-1, and MUM-1 and disease progression in cases of MM and MGUS. Materials and Methods: Immunohistochemical staining for CD138, Pan-Ras, CCL-3, DKK-1, and MUM-1 were performed on bone marrow biopsy samples from 94 MM and 20 MGUS patients diagnosed between 2011 and 2018. Immunohistochemical results were examined semiquantitatively, and the associations between the immunohistochemical, clinical, and biochemical markers utilized for MM and MGUS patient staging were analyzed. Results: Pan-Ras, DKK-1, and MUM-1 staining results were significantly higher in MM compared to MGUS (p=0.005, 0.001, and 0.001, respectively). The mean CCL-3 expression in patients with MGUS was 23.15%, while it was 18.68% in cases of MM (p=0.413). CCL-3 expression was significantly higher in high-risk MGUS cases compared to other risk groups according to the Mayo Clinic Risk Stratification for MGUS. According to the International Staging System and the Revised International Staging System, CD138 expression was higher among stage II and stage III patients than stage I patients. Conclusion: Differences in Pan-Ras, MUM-1, DKK-1, and CCL-3 expressions between MM and MGUS suggest that these molecules may play a role in the progression of MGUS to MM. CCL-3, an immunohistochemical marker, may be predictive of MGUS progression, while CD138 is associated with more advanced stages of MM. Amaç: Multipl myelom (MM) ve MM’nin prekürsörü olan önemi belirsiz monoklonal gamopati (MGUS), plazma hücreli neoplazilerdir. Güncel çalışmalarda bu hastalıkların etiyopatogenezini aydınlatmak, spesifik tedavi ajanları ve prognostik belirteçler geliştirmek için multidisipliner çalışmalar yürütülmektedir. Çalışmamızda MM ve MGUS’lerde CD138, Pan-Ras, CCL-3, DKK-1 ve MUM1 immünoekspresyonun hastalık evreleriyle olan ilişkisini araştırmayı hedefledik. Gereç ve Yöntemler: 2011-2018 yılları arasında tanı alan 94 MM ve 20 MGUS olgusuna ait kemik iliği biyopsilerine, CD138, Pan-Ras, CCL-3, DKK-1, MUM-1 immünohistokimyasal (İHK) boyaması yapıldı. İHK sonuçları semi kantitatif olarak değerlendirildi ve MM ve MGUS olgularının hastalık evreleriyle olan ilişkileri değerlendirildi. Bulgular: Pan-Ras, DKK-1 ve MUM-1 immünoekspresyonu, MM’li olgularda MGUS’li olgulara göre anlamlı olarak daha yüksek saptandı (p=0,005, 0,001, ve 0,001, sırasıyla). MGUS olgularında ortalama CCL-3 immünoekspresyonu %23,15 iken, MM olgularında %18,68 idi (p=0,413). MGUS olgularında Mayo Klinik risk sınıflandırması (MCRS) modeline göre, yüksek riskli MGUS olgularında diğer risk gruplarına kıyasla CCL-3 ekspresyonu önemli ölçüde artmış olarak saptandı. CD138 ekspresyonu, ISS ve R-ISS sınıflama sistemlerine göre, evre 2 ve evre 3 hastalarda evre 1 hastalara göre artmış olarak tespit edildi. Sonuç: MM ve MGUS olgularında Pan-Ras, MUM-1, DKK-1 ve CCL-3 ekspresyonlarındaki farklılıklar, bu belirteçlerin MGUS-MM progresyonunda önemli roller üstlendiğini göstermektedir. Kemik iliği biyopsilerinde, kolay ve pratik bir şekilde, CCL-3 immün belirteci MGUS progresyonunda prediktif; CD138 ise MM olgularında ileri evre tayininde kullanılabilir.Publication Open Access Investigation of typhlitis in bone marrow transplant patients in a stem cell transplant unit(2022-08-01) TOPTAŞ, TAYFUR; Deveci B., Kublashvili G., Yilmaz S., Ozcan B., Korkmaz H. F. , Gursoy O., TOPTAŞ T., Dosemeci L., Saba R.Typhlitis is a special type of enterocolitis that specifically develops in immunosuppressive patients with hematological malignancies. Typhlitis is a common consideration after bone marrow transplantation due to high-dose chemotherapy that is used in conditioning regimens those contain high-dose cytotoxic chemotherapeutic agents. Although there are several studies about typhlitis during chemotherapy or in leukemia patients, there is not enough data evaluating its relationship between stem cell transplant in adults. Therefore, the current study aimed to analyze the possible causes that may lead to the development of typhlitis in hematopoietic stem cell recipient patients. This retrospective study included 210 adult patients who underwent bone marrow transplantation between January 2017 and December 2019. Pediatric patients (patients younger than 18 years of age) were excluded. Patients\" data were evaluated to determine their effects on typhlitis and the mortality risk of the patients with typhlitis. The analysis of the variables was performed using the IBM SPSS Statistics for Windows version 26 (IBM Corp., Armonk, NY).Variables were analyzed at a 95% confidence level and a P value <0.05 was considered significant. Typhlitis developed in 23 (10.9%) transplant patients. Male sex, length of hospital stay, presence of febrile neutropenia, antibiotic and antifungal use, need for switching antibiotics, duration of neutropenia, diarrhea and antibiotic use in days were risk factors for development of typhlitis. It was observed that 100-days mortality was higher in typhlitis group reaching to a statistical significance (P < .05). In multiple logistic regression analysis, presence of mucositis and additional source of infection were determined as independent risk factors for the development of typhlitis in bone marrow transplant patients. This study provides valuable information for bone marrow transplant patients through an analysis of risk factors for the development of typhlitis. According to our results, mucositis and additional bacterial infections were found as risk factors for typhlitis therefore it would be beneficial for clinicians to consider these factors in patient follow-up. However, due to the retrospective nature of our study, prospective studies are needed to investigate risk factors and optimum treatment methods for typhlitis.Publication Metadata only Publishing in hematology journals: A Scientometric and economic evaluation(2020-12-01) TOPTAŞ, TAYFUR; Tazegul G., Atas U., Ulas T., TOPTAŞ T., SALİM O.Introduction: Herein, we aimed to compare the scientometric data of hematology journals, and compare the publication models, especially the scientometric data of journals with all-open access (OA) and hybrid-OA publication models.Publication Metadata only Patient characteristics and management practices in chronic myeloid leukemia in Turkey: reflections from an expert meeting(2022-01-01) TOPTAŞ, TAYFUR; EŞKAZAN A. E., ALİ R., Alnigenis E., Ayyildiz O., Haznedaroglu I., Kirkizlar O., Kurtoglu E., Malhan S., Oksuz E., Polat O., et al.Introduction The therapeutic landscape of chronic myeloid leukemia (CML) has evolved significantly since the introduction of imatinib. The European LeukemiaNet (ELN) recommendations serve as a guide for diagnosis, treatment, and monitorization of CML, but availability and accessibility of diagnostic tools and medications affect their applicability. Areas covered This article provides an overview of the current clinical management of CML in Turkey with reference to the key outputs of the online expert meeting held in November 2020. The applicability of the ELN 2020 recommendations for treating CML in clinical practice was also discussed. Expert opinion Imatinib is the only reimbursed and the most preferred first-line treatment in CML restricting the upfront use of second-generation tyrosine kinase inhibitors (TKIs), thereby limiting the applicability of treatment-free remission approach in Turkey. The ELN recommendations about using the EUTOS Long-Term Survival (ELTS) score for risk assessment and focusing on patient reported outcomes and quality of life can be enhanced with educational activities. The widespread availability of standardized technical infrastructure for diagnosing and monitoring CML will contribute to better disease management. Establishing a sustainable national database for CML is valuable for observing patient characteristics and disease outcomes as well as the impact of treatment patterns over time.Publication Open Access Hereditary hyperferritinemia-cataract syndrome in a family with HFE-H63D mutation(2023-03-01) YANIK, AHMET MERT; YILMAZ, ASU FERGÜN; TOPTAŞ, TAYFUR; Eris T., YANIK A. M., Demirtas D., Yilmaz A. F., TOPTAŞ T.Hereditary hyperferritinemia-cataract syndrome (HHCS) is a rare genetic condition characterized by persistent hyperferritinemia (usually ferritin >1,000 ng/mL) without tissue iron overload, with or without early-onset slow-progressing bilateral nuclear cataract. It was first identified as a new genetic disorder in 1995, and since then genetic sequencing studies have been carried out to identify associated mutations in affected families. New mutations around the world are still being reported in the iron-responsive element (IRE) of the L-ferritin gene (FTL) to this day. Many clinicians remain unaware of this rare condition. The co-occurrence of FTL mutations and hereditary hemochromatosis (HH) mutations, especially H63D, on the HFE gene has been reported in the literature, which often leads to a diagnosis of HH, missed diagnosis of HHCS, incorrect treatment with phlebotomies and the occurrence of associated iatrogenic iron deficiency anemia. We herein report the case of a 40-year-old woman with spontaneous facial freckling, bilateral cataracts, homozygosity for HFE H63D mutation, iron deficiency anemia, and hyperferritinemia, who has been treated with phlebotomy and iron chelation therapy to no avail. Eleven years after being diagnosed and treated for HH, a reevaluation of her clinical presentation, laboratory results, medical imaging, and family history led to the recognition that her case is explained not by HH, but by an alternative diagnosis, HHCS. Our main objective in this report is to increase clinical awareness about HHCS, an often-unknown differential diagnosis of hyperferritinemia without iron overload, and to prevent adverse medical interventions in HHCS patients.Publication Metadata only Impact of autologous stem cell transplantation on survival outcomes in patients with peripheral T cell lymphoma(2022-01-01) TOPTAŞ, TAYFUR; ORUÇ, ÖZEN; ERCAN, TARIK; Guren C. U. , TOPTAŞ T., MEHTAP Ö., Yılmaz G., Polat G., ORUÇ Ö., ERCAN T., Arikan F., Yilmaz F., Atagunduz I. K. , et al.© 2022 Elsevier LtdData about the timing of autologous stem cell transplantation (ASCT) in peripheral T cell lymphoma (PTCL) are conflicting. We aimed to investigate the impact of the sequence of ASCT on the survival outcomes in patients with PTCL. Analyzes were performed retrospectively in a total of 81 patients, 16 of whom underwent upfront ASCT and 12 received salvage ASCT. In univariate analysis, upfront ASCT reduced the risk of progression and death by 77% (Hazard ratio (HR): 0.23, 95% confidence interval (CI): 0.09–0.60) (p = 0.003) and by 84% (HR: 0.16, 95% CI: 0.5–0.55) (p = 0.003), respectively. However, in multivariate analysis, only salvage ASCT predicted a more favorable progression-free and overall survival (HR: 0.17, 95% CI: 0.06–0.48, p = 0.001 and HR: 0.20, %95 GA: 0.06–0.62, p = 0.005, respectively). In conclusion, regardless of first-line therapy, patients have more favorable outcomes if they receive salvage ASCT. Upfront ASCT does not add clinically significant benefit to survival outcomes.Publication Metadata only Glofitamab in relapsed/refractory diffuse large B-cell lymphoma: Real-world data(2023-05-01) TOPTAŞ, TAYFUR; Atesoglu E. B., Gulbas Z., Uzay A., ÖZCAN M., ÖZKALEMKAŞ F., Dal M. S., Kalyon H., Akay O. M., Deveci B., Bekoz H., et al.Glofitamab is a CD3xCD20 bi-specific antibody with two fragments directed to the CD20 antigen and a single CD3-binding fragment. Encouraging response and survival rates were recently reported in a pivotal phase II expansion trial conducted in patients with relapsed/refractory (R/R) B-cell lymphoma. However, the real-world data of patients of all ages with no strict selection criteria are still lacking. Herein, this retrospective study aimed to evaluate the outcomes of diffuse large B-cell lymphoma (DLBCL) patients who received glofitamab via compassionate use in Turkey. Forty-three patients from 20 centers who received at least one dose of the treatment were included in this study. The median age was 54 years. The median number of previous therapies was 4, and 23 patients were refractory to first-line treatment. Twenty patients had previously undergone autologous stem cell transplantation. The median follow-up time was 5.7 months. In efficacy-evaluable patients, 21% and 16% of them achieved complete response and partial response, respectively. The median response duration was 6.3 months. The median progression-free survival (PFS) and overall survival (OS) was 3.3 and 8.8 months, respectively. None of the treatment-responsive patients progressed during the study period, and their estimated 1-year PFS and OS rate was 83%. The most frequently reported toxicity was hematological toxicity. Sixteen patients survived, while 27 died at the time of the analysis. The most common cause of death was disease progression. One patient died of cytokine release syndrome during the first cycle after receiving the first dose of glofitamab. Meanwhile, two patients died due to glofitamab-related febrile neutropenia. This is the largest real-world study on the effectiveness and toxicity of glofitamab treatment in R/R DLBCL patients. The median OS of 9 months seems promising in this heavily pretreated group. The toxicity related mortality rates were the primary concerns in this study.Publication Open Access Comparative efficacy and safety of beam and team conditioning regimens for autologous stem cell transplantation in lymphoma patients(2023-02-20) TOPTAŞ, TAYFUR; Deveci B., Atesoglu E. B., Bayrak E., Kublashvili G., TOPTAŞ T., Saba R., Gulbas Z.Background. Conditioning regimens with high-dose chemotherapy and autologous stem cell transplantation (ASCT) are the mainstays of treatment in lymphoma patients. Although the most frequently used conditioning regimen is the BEAM regimen (Carmustine, Etoposide, Cytarabine, and Melphalan), and alternatives are also used in certain circumstances. The TEAM regimen (carmustine is substituted by the alkylating agent thiotepa) is one of these alternatives; however, data regarding the comparisons of efficacy and safety profiles of these 2 regimens is scarce. This study compared the outcomes of patients who received conditioning regimens with BEAM and TEAM and underwent an ASCT.Methods. This study was conducted as a retrospective assessment of 294 patient outcomes in terms of efficacy and safety. Adult patients with lymphoma diagnosis who received BEAM or TEAM conditioning regimens and underwent an ASCT between January 1, 2016 and December 31, 2019 were included in the analyses.Results. A total of 294 patients (median age at ASCT: 50 years, males: 60.5%, diffuse large B-cell lymphoma: 35%) were included. Eighty patients (27.2%) received the TEAM regimen, and 214 (72.8%) received the BEAM regimen. Regarding safety profiles, the thrombocyte engraft-ment time was significantly higher in the TEAM group (P = .003) and fever of unknown etiology was significantly higher in the BEAM group (P = .042). Also, nausea was more in the TEAM group (P = .031). The complete remission rate was 57.5% and 70.3% in the TEAM and BEAM regimens, respectively. The overall mortality rate was 37.3% and not significantly different between the groups (43% and 35% in the TEAM and BEAM groups, P = .22) over a similar median follow-up of 1667 days (P = .28). The 3-year survival rate was 66% and 67% and the 5-year survival rate was 52% and 58% in the TEAM and BEAM regimens, respectively, without significant difference.Conclusion. To the best of our knowledge, this is one of the few studies in the literature that compared the TEAM and BEAM as conditioning regimens for ASCT in lymphoma patients. The 2 regimens may provide similar overall survival outcomes and have a comparable safety pro-file. Although the BEAM regimen may be associated with longer progression-free survival times, the difference may be covered by the similar survival after ASCT.Publication Open Access The role of ruxolitinib treatment in JAK-mutated Ph-like acute lymphoblastic leukemia(2023-01-01) DEMİRTAŞ, DERYA; YANIK, AHMET MERT; ATAGÜNDÜZ, IŞIK; TOPTAŞ, TAYFUR; Candan O., Demirtas D., YANIK A. M., ATAGÜNDÜZ I., TOPTAŞ T.Publication Open Access Peripheral T-Cell Lymphoma Coexisting with Autoimmune Hemolytic Anemia: Analysis of Clinical Features(2024-01-01) DEMİRTAŞ, DERYA; YANIK, AHMET MERT; YILMAZ, ASU FERGÜN; ATAGÜNDÜZ, IŞIK; TUĞLULAR, AYŞE TÜLİN; TOPTAŞ, TAYFUR; Candan O., Naghizada N., DEMİRTAŞ D., YANIK A. M., Salim S., Menguc M. U., Arikan F., YILMAZ A. F., ATAGÜNDÜZ I., TUĞLULAR A. T., et al.Autoimmune hemolytic anemia (AIHA) is characterized by the production of antibodies targeting red blood cells (RBCs) antigens. The diagnosis is based on the presence of a hemolytic anemia with a positive direct antiglobulin test (or Coombs test) and on the absence of any other hereditary or acquired cause of hemolysis, although direct antiglobulin test-negative cases are not quite uncommon (5% of 308 cases of AIHA recently reported by the Gruppo Italiano Malattie EMatologiche dell’Adulto [GIMEMA]) [1, 2]. AIHA can present in primary and secondary forms. Secondary AIHA generally includes factors such as connective tissue diseases, drugs, infections, and lymphomas [3]. Cases of AIHA accompanied by lymphoma are rare and are typically presented in the literature as case reports. Roughly one-fifth of AIHA patients have lymphoma, while 7–10% of lymphoma patients have co-existing AIHA, indicating a clinicopathological link between both diseases [4–6]. In clinical settings, AIHA is commonly associated with indolent B-cell lymphomas, whereas the combination of AIHA with peripheral T-cell lymphoma (PTCL) is rarely observed [7–11]. This study retrospectively analyzes the clinical data, laboratory characteristics, treatment processes, and prognosis of five patients with the coexistence of PTCL and AIHA who were diagnosed within the last 10 years in our center.