Tıp Fakültesi / Faculty of Medicine

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    Assessment of Stem Cell Transplant Eligibility in Recipients with Oral Foci of Infection: Appropriate Conditioning Regimens
    (2023) Boga, Can; Sisli, Selen Nihal; Bahar, Abdul Rasheed; Tamer, Yusuf; Kasar, Mutlu; Bascil, Sibel; Ozdogu, Hakan; Asma, Suheyl; Demiroglu, Yusuf Ziya; Yeral, Mahmut; 0000-0002-0225-2477; 37341460; ADG-7352-2022
    Objectives: It is unclear whether patients with oral foci of infection should be approved for hematopoietic stem cell transplant with or without posttransplant cyclophosphamide. We compared the presence of oral foci of infection status on the effects of various conditioning regimens for such patients.Materials and Methods: Three groups were classified as autologous (carmustine-etoposide-cytarabinemelphalan, mitoxantrone-melphalan, and melphalan 200 mg/m2 groups; n = 502 patients), and 6 groups were classified as allogeneic (busulfan-fludarabinerabbit anti-T-lymphocyte globulin, busulfanfludarabine-posttransplant cyclophosphamide, fludarabine-cyclophosphamide-anti-T-lymphocyte globulin, busulfan-fludarabine-anti-T-lymphocyte globulin-posttransplant cyclophosphamide, total body irradiation-posttransplant cyclophosphamide, and other; n = 428 patients). Data were collected from a database that met international accreditation requirements. We evaluated dental radiological findings and calculated interobserver reliability.Results: Oral foci of infections increased febrile neutropenia and bacterial infection frequencies in both groups but only increased mucositis frequency in patients with allogeneic treatment. The frequencies of oral foci of infection-related complications were similar in both the autologous and allogeneic groups. Rate of graft-versus-host disease was not affected by oral foci of infection status. Periodontitis/cysts and periapical lesions increased the risk of infections at day 100 in the mitoxantrone-melphalan group versus the melphalan 200 mg/m2 group. We observed no differences among the autologous transplant groups in terms of early mortality. Similarly, no differences in early mortality were observed among the allogeneic groups.Conclusions: Transplant is a valid option in patients with oral foci of infections undergoing various autologous and allogeneic transplant protocols when time is of the essence, even at myeloablative dose intensities.
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    Graft-Versus-Host Disease and Relapse/Rejection-Free Survival After Allogeneic Transplantation for Idiopathic Severe Aplastic Anemia: A Comprehensive Analysis from the SAAWP of the EBMT
    (2023) Devillier, Raynier; Eikema, Dirk-Jan; Dufour, Carlo; Aljurf, Mahmoud; Wu, Depei; Maschan, Alexei; Kulagin, Alexander; Halkes, Constantijn J. M.; Collin, Matthew; Snowden, John; Renard, Cecile; Ganser, Arnold; Sykora, Karl-Walter; Gibson, Brenda E.; Maertens, Johan; Itala-Remes, Maija; Corti, Paola; Cornelissen, Jan; Bornhaeuser, Martin; Colorado Araujo, Mercedes; Ozdogu, Hakan; Risitano, Antonio; Socie, Gerard; de latour, Regis Peffault; 36951165
    Survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe idiopathic aplastic anemia (SAA) has improved in recent years, approaching 75% at 5 years. However, an SAA-adapted composite endpoint, graft-versus-host disease (GvHD) and relapse/rejection-free survival (GRFS), may more accurately assess patient outcomes beyond survival. We analyzed GRFS to identify risk factors and specific causes of GRFS failure. Our retrospective analysis from the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation included 479 patients with idiopathic SAA who underwent allo-HSCT in two conventional situations: i) upfront allo-HSCT from a matched related donor (MRD) (upfront cohort), and ii) allo-HSCT for relapsed or refractory SAA (rel/ref cohort). Relevant events for GRFS calculation included graft failure, grade 3-4 acute GvHD, extensive chronic GvHD, and death. In the upfront cohort (n=209), 5-year GRFS was 77%. Late allo-HSCT (i.e., >6 months after SAA diagnosis) was the main poor prognostic factor, specifically increasing the risk of death as the cause of GRFS failure (hazard ratio [HR]=4.08; 95% confidence interval [CI]: 1.41-11.83; P=0.010). In the rel/ref cohort (n=270), 5-year GRFS was 61%. Age was the main factor significantly increasing the risk of death (HR=1.04; 95% CI: 1.02-1.06; P<0.001), acute GvHD (HR=1.03; 95% CI: 1.00-1.07; P=0.041), and chronic GvHD (HR=1.04; 95% CI: 1.01-1.08; P=0.032) as the cause of GRFS failure. GRFS after upfront MRD allo-HSCT was very good, notably with early allo-HSCT, confirming that younger patients with an MRD should be transplanted immediately. GRFS was worse in cases of salvage allo-HSCT, most notably in older patients, questioning the utility of allo-HSCT earlier in the disease course.
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    Prophylactic Red Blood Cell Exchange May Be Beneficial in the Management of Sickle Cell Disease in Pregnancy
    (2015) Asma, Suheyl; Kozanoglu, Ilknur; Tarim, Ebru; Sariturk, Cagla; Gereklioglu, Cigdem; Akdeniz, Aydan; Kasar, Mutlu; Turgut, Nurhilal H.; Yeral, Mahmut; Kandemir, Fatih; Boga, Can; Ozdogu, Hakan; 0000-0002-5268-1210; 0000-0002-8902-1283; 0000-0003-3856-7005; 0000-0001-5335-7976; 0000-0002-9580-628X; 0000-0002-4130-1059; 0000-0002-9680-1958; 25070465; AAE-1241-2021; AAD-5542-2021; AAL-3906-2021; AAI-7831-2021; ABC-4148-2020; AAD-6222-2021; AAS-7129-2021
    BackgroundSickle cell disease (SCD) is associated with chronic hemolysis and painful episodes. Pregnancy accelerates sickle cell complications, including prepartum and postpartum vasoocclusive crisis, pulmonary complications, and preeclampsia or eclampsia. Fetal complications include preterm birth and its associated risks, intrauterine growth restriction, and a high rate of perinatal mortality. The purpose of this study was to evaluate pregnancy outcomes in patients with SCD who underwent planned preventive red blood cell exchange (RBCX). Study Design and MethodsWe retrospectively evaluated the complications of SCD in 37 pregnant patients. Patients with SCD who had undergone prophylactic RBCX were compared with a control group who had not undergone RBCX during pregnancy. ResultsForty-three exchange procedures were performed in 24 patients. The control group comprised 13 patients with a mean age of 27.43.3 years who had not undergone RBCX during pregnancy. Four of the five patients who developed a vasoocclusive crisis died. There was a significant difference in maternal mortality between the study and control groups (p=0.011). There was also a significant difference in the incidence of vasoocclusive crisis between the study and control groups. One fetal death occurred in the 20th gestational week in a patient in the control group, although there were no postpartum complications in either the babies or the mothers in the control group. ConclusionThis study has demonstrated that prophylactic RBCX during pregnancy is a feasible and safe procedure for prevention of complications. Given the decrease in the risks of transfusion, RBCX warrants further study.
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    Plasma-Exchange Treatment for Severe Carbamazepine Intoxication: A Case Study
    (2014) Kozanoglu, Ilknur; Kahveci, Suat; Asma, Suheyl; Yeral, Mahmut; Noyan, Aytul; Boga, Can; Ozdogu, Hakan; https://orcid.org/0000-0002-5268-1210; https://orcid.org/0000-0001-5335-7976; https://orcid.org/0000-0002-9580-628X; https://orcid.org/0000-0002-8902-1283; 24136443; AAE-1241-2021; AAI-7831-2021; ABC-4148-2020; AAD-5713-2021; AAD-6222-2021; AAD-5542-2021
    Acute poisoning is an important cause of morbidity and mortality during childhood. This manuscript reports the positive outcome of a pediatric case with a history of accidental carbamazepine intake treated using plasma exchange. A 3-year-old male presented with severe carbamazepine intoxication. He was comatose and had generalized tonic clonic seizure, ventricular tachycardia, and hypotension. Although he did not respond to classical therapies, we performed two sessions of plasma exchange. The patient recovered rapidly and was discharged from the hospital six days from the time of carbamazepine ingestion with no complication or neurologic impairment. Plasma exchange can be performed safely in very small children, and it might be the first line treatment, particularly for intoxication with drugs that have high plasma-protein-binding properties. (C) 2013 Wiley Periodicals, Inc.
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    Clinical Significance of Circulating Blood and Endothelial Cell Microparticles in Sickle-Cell Disease
    (2014) Kasar, Mutlu; Boga, Can; Yeral, Mahmut; Asma, Suheyl; Kozanoglu, Ilknur; Ozdogu, Hakan; https://orcid.org/0000-0003-3856-7005; https://orcid.org/0000-0002-9680-1958; https://orcid.org/0000-0002-9580-628X; https://orcid.org/0000-0001-5335-7976; https://orcid.org/0000-0002-5268-1210; https://orcid.org/0000-0002-8902-1283; 24254379; AAL-3906-2021; AAD-6222-2021; ABC-4148-2020; AAI-7831-2021; AAE-1241-2021; AAD-5542-2021
    Increased thrombocyte activation leads to a higher likelihood of coagulation in sickle-cell disease. On the other hand, chronic inflammation and endothelial cell activation promote vaso-occlusion. The effect of circulating microparticles derived from erythrocytes, monocytes, thrombocytes, and endothelial cells on the vaso-occlusive process is unclear. This study aims to analyze the relationship between sickle-cell disease and miscellaneous organ complications by defining the circulating microparticles during the steady-state and painful crisis periods in 45 patients with sickle-cell disease. Microparticle analysis was conducted using an eight-parameter flow cytometric method, using CD61 PERCP, CD142PE, CD106 FITC, CD14 APC-H7, CD235a FITC, and Annexin-V APC monoclonal antibodies. Microparticle levels of sickle-cell patients were found to be significantly higher during both painful crisis and steady-state situations compared with the control group (for all, p < 0.001). Among these microparticles, levels of erythrocyte microparticles (eMPs) were significantly higher during crisis than in the steady-state period (eMP steady state vs. painful crisis: 7.59 +/- 12.24 vs. 7.59 +/- 12.24, respectively; p < 0.01). Microparticles, including eMPs, were not affected by hydroxyurea treatment. Their level did not reflect the high frequency of crisis (>3 times/year). Thrombocyte microparticle levels were found to be higher in patients with nephropathia than in those without ( 48.05 +/- 40.23 vs. 7.67 +/- 6.75, respectively; p < 0.049). Circulating microparticles seem to be involved in the pathogenesis of sickle-cell disease. eMPs may help with the management of crisis. Thrombocyte microparticles might predict renal damage induced by vaso-occlusion.
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    An Unusual Cause of Febrile Neutropenia: Brucellosis
    (2014) Solmaz, Soner; Asma, Suheyl; Ozdogu, Hakan; Yeral, Mahmut; Turunc, Tuba; https://orcid.org/0000-0001-5335-7976; https://orcid.org/0000-0002-8902-1283; https://orcid.org/0000-0002-9580-628X; 25492662; AAI-7831-2021; AAD-5542-2021; ABC-4148-2020
    Febrile neutropenia which is a common complication of cancer treatment, is one of the major causes of morbidity and mortality. Several gram-negative and gram-positive bacteria are responsible for infections in neutropenic patients, however the most common microorganisms are Escherichia coli and coagulase-negative staphylococci, in decreasing order. Although Brucella spp. infections are endemic in Turkey, brucellosis-related febrile neutropenia has only rarely been reported. In this report, a case of brucellosis-related febrile neutropenia in a patient with acute myeloblastic leukemia (AML) was presented. A 56-year-old male patient presenting with fever, petechiae/purpura, leukocytosis, thrombocytopenia, and anemia was admitted to our hospital. Laboratory studies revealed a hemoglobin level of 8.27 g/dl, leukocyte count of 77.100 k/ml, absolute neutrophil count of 200 k/ml, and platelets at 94.200 k/ml. The patient was diagnosed as AML-M1 and piperacillin/tazobactam was started as the first-line antibiotic therapy due to the febrile neutropenia. On admission, blood and urine cultures were negative. Once the fever was controlled, remission/induction chemotherapy was initiated. However, fever developed again on the eight day, and vancomycin was added to the therapy. Since the fever persisted, the antibiotic therapy was gradually replaced with meropenem and linezolid. However, fever continued and the patient's general condition deteriorated. Subsequently performed Brucella tube agglutination test revealed positivity at 1/320 titer and the microorganism grown in blood culture (Bactec 9050; BD, USA) was identified as B.melitensis by conventional methods. Rifampicin and doxycycline therapy was started immediately, however, the patient died due to septic shock. If the tests for brucellosis were performed earlier when response to second step antibiotic therapy lacked in this patient, it was assumed that mortality could be prevented by the prompt initiation of the appropriate treatment. Thus, since brucellosis is endemic in Turkey, it should be considered as a possible agent of febrile neutropenia especially in patients unresponsive to empiric antibiotherapy and appropriate diagnostic tests should be performed.
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    Clinical Relevance of Apheretic Graft Composition in Patients With Acute Myeloblastic Leukemia Who Received a Busulfan-Fludarabine-Antithymocyte Globulin Conditioning Regimen for Allogeneic Transplant
    (2015) Yeral, Mahmut; Kasar, Mutlu; Boga, Can; Kozanoglu, Ilknur; Ozdogu, Hakan; Sariturk, Cagla; 0000-0002-4130-1059; 0000-0002-9580-628X; 0000-0002-9680-1958; 0000-0002-8902-1283; 0000-0003-3856-7005; 0000-0002-5268-1210; 26103468; AAS-7129-2021; ABC-4148-2020; AAD-6222-2021; AAD-5542-2021; AAL-3906-2021; AAE-1241-2021
    Objectives: Sparse data are available about the effects of apheretic graft composition on the clinical transplant outcome in allotransplanted patients who have hematologic malignant disease. Major obstacles in recent studies have included heterogeneity of patient populations and differences in the conditioning regimens used. Materials and Methods: This prospective study included 50 patients who had acute myeloblastic leukemia and received busulfan-fludarabine-antithymocyte globulin -based conditioning for peripheral allogeneic stem cell transplant. The concentration of CD34+ cells, T-cell subsets, B cells, and natural killer cells in the graft were analyzed by flow cytometry in the donors who were matched for human leukocyte antigen. Results: In univariate analysis, infusion with a higher dose of natural killer cells (> 1.55 x 10(6)/kg) was associated with improved survival (P=.007 for disease-free survival; P=.024 for overall survival) in patients with acute myeloblastic leukemia. Cox regression models revealed that increased concentration of natural killer cells and CD34+ cells positively affected the clinical outcome of allotransplanted patients (P =.005 for both cell types). According to univariate analysis, these findings were dependent on minimal residual disease and acute graft-versus-host disease. Graft versus-host disease (acute and chronic forms) was not affected by graft composition. Conclusions: Our results suggest that increased concentration of natural killer cells and CD34+ cells in the apheretic product may predict better survival. In contrast, busulfan-fludarabine-antithymocyte globulin -based conditioning eliminates the disadvantages that resulted from the high content of T-cell subsets and B cells, and the course of the transplant and clinical parameters were not affected by the amount of T and B cells.
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    Total Body Irradiation Plus Fludarabine Versus Busulfan Plus Fludarabine As A Myeloablative Conditioning for Adults with Acute Myeloid Leukemia Treated with Allogeneic Hematopoietic Cell Transplantation. A Study on Behalf of The Acute Leukemia Working Party of The EBMT
    (2022) Swoboda, Ryszard; Labopin, Myriam; Giebel, Sebastian; Schroeder, Thomas; Kroeger, Nicolaus; Arat, Mutlu; Savani, Bipin; Spyridonidis, Alexandros; Hamladji, Rose-Marie; Potter, Victoria; Berceanu, Ana; Yakoub-Agha, Ibrahim; Rambaldi, Alessandro; Ozdogu, Hakan; Sanz, Jaime; Nagler, Arnon; Mohty, Mohamad; 36460819
    Cyclophosphamide is frequently substituted with fludarabine (Flu) in conditioning regimens before allogeneic hematopoietic cell transplantation (allo-HCT). We aimed to compare retrospectively, total body irradiation (12 Gy) plus Flu (FluTBI12) versus busulfan (Bu) plus Flu (FB4) as a myeloablative conditioning before allo-HCT in patients with acute myeloid leukemia (AML). Out of 3203 patients who met the inclusion criteria, 109 patients treated with FluTBI12 and 213 treated with FB4 were included in a final matched-pair analysis. In both groups, median patient age was 41 years, first or second complete remission (CR1/CR2) proportion was 78%/22%, allo-HCT from an unrelated donor was performed in 78% of patients. The probabilities of leukemia-free survival and overall survival at 2 years in FluTBI12 and FB4 groups were 65% vs. 60% (p = 0.64) and 70% vs. 72% (p = 0.87), respectively. The cumulative incidence of relapse was 19% vs. 29% (p = 0.11), while non-relapse mortality was 16% vs. 11%, respectively (p = 0.13). There were no statistical differences in both acute and chronic graft-versus-host disease (GVHD) incidence. The probability of GVHD-free, relapse-free survival (GRFS) was 49% for both groups. FluTBI12 and FB4 are comparable myeloablative regimens before allo-HCT in AML patients transplanted in CR1 and CR2.
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    QTc Prolongation During Peripheral Stem Cell Apheresis in Healthy Volunteers
    (2017) Korur, Asli; Kozanoglu, Ilknur; Buyukkurt, Nurhilal; Yeral, Mahmut; Kandemir, Fatih; Gereklioglu, Cigdem; Sariturk, Cagla; Asma, Suheyl; Solmaz, Soner; Boga, Can; Ozdogu, Hakan; 0000-0002-5086-5593; 0000-0001-5335-7976; 0000-0002-8902-1283; 0000-0002-5268-1210; 0000-0002-9580-628X; 0000-0002-4130-1059; 0000-0002-0895-4787; 0000-0002-9680-1958; 27543914; AAD-5616-2021; AAI-7831-2021; AAD-5542-2021; AAD-6222-2021; AAE-1241-2021; ABC-4148-2020; AAS-7129-2021; AAE-1457-2021
    Background and aim: Today, voluntary donation of peripheral blood stem cells by healthy donors for allogeneic hemopoietic cell transplantation is common worldwide. Such donations are associated with small but measurable risks of morbidity and mortality. Most complications are associated with citrate infusion during cell collection. We studied the effects of citrate infusion on the QTc and other vital parameters during and after peripheral stem cell apheresis in volunteers. Method: To ensure that donors were healthy, screening included taking a detailed medical history, physical examination, and laboratory measurements of plasma calcium and magnesium. Corrected QT (QTc) values were assessed using a 12-lead electrocardiographic platform that derived QTc values automatically. Results: In all, 141 apheresis procedures were performed. The mean QTc values at baseline, at 2 and 4 h during the procedure, and at 30 min after the procedure, were 347.6 +/- 59.5, 349.9 +/- 52.8, 391.8 +/- 54.0, and 404.8 +/- 59.2 ms, respectively. The baseline and 2 h QTcs did not differ significantly, but the baseline QTc did differ significantly from the 4 h and 30 min after the procedure values. The plasma levels of calcium and magnesium did not significantly differ before and after the procedure. Conclusion: QTc prolongation may develop during leukopheresis, particularly if the procedure takes more than 2 h. Thus, to enhance donor safety, QTc measurement should be standard for all donors. In addition, any family history of sudden death should be noted, to prevent the development of possible fatal arrhythmia in susceptible donors.
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    Pregnancy and Sickle Cell Disease: A Review of the Current Literature
    (2016) Boga, Can; Ozdogu, Hakan; https://orcid.org/0000-0002-8902-1283; 26672916; AAD-6222-2021; AAD-5542-2021
    Sickle cell disease (SCD) is the most common hereditary disease worldwide, presenting with anemia and intermittent severe pain. Pregnancy in a patient with SCD is associated with high levels of maternal and fetal morbidity and mortality; the maternal and fetal death rates during pregnancy can attain 11.4% and 20%, respectively. Patient care has improved over time. However, certain management issues remain unresolved; these include the optimum policy in terms of prophylactic blood transfusion, and the use of antiplatelet drugs. Such issues are attributable to the heterogeneous nature of clinical SCD features, and the limitations of uncontrolled and prospective trials. In this review, we seek to facilitate a better understanding of relevant issues via creation of a comparative data profile extracted from current studies. This report may also encourage the drafting of standard operating procedure for management of pregnancy in SCD patients. (C) 2015 Elsevier Ireland Ltd. All rights reserved.