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    A comparison of hypersensitivity reactions between intravenous and intramuscular applications of native E. coli asparaginase in children with acute lymphoblastic leukemia
    (2023) Odaman Al, Işık; Özdemir, Nihal; Zengin Ersoy, Gizem; Bayram, Cengiz; Çilengiroğlu, Özgül Vupa; Arslantaş, Esra; Paslı Uysalol, Ezgi; Ayçiçek, Ali
    Introduction: Asparaginase is an indispensable drug in treating childhood acute lymphoblastic leukemia (ALL). Hypersensitivity reactions (HSR) are the most common side effects and interfere with the antineoplastic activity of the drug. This study aims to compare the intramuscular (IM) and intravenous (IV) administration routes of Native Escherichia coli Lasparaginase (L-ASNase) in terms of hypersensitive reactions. Methods: L-ASNase was randomly administered IV or IM to newly diagnosed ALL patients and HSR was monitored in all patients for 1 h following the end of the IV infusion and for 2 h following the end of the IM administration of L-ASNase. Based on a retrospective review of clinical charts, reactions were identified. In order to determine the severity of each allergic reaction, we used the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 for allergic reactions. Results: A total of 1032 doses of L-ASNase were administered to 85 patients (42 males and 43 females) during the study period. Among 85 patients, 30 reactions were recorded, which means that 35% of the patients reacted. According to the CTCAE, twenty-nine out of 30 reactions (97%) were grade 2, while one (3%) was grade 4. In terms of individual doses, there was a non-significant trend toward increased incidence of reactions with IV administration (3.8% versus 0.9%, p = 0.064). The rate of reactions was higher in patients who received all IV doses (n: 60) as compared to those who received all IM doses (n: 25) (31.7% vs. 3.5%; chi-square= 8.415, p value=0.04). Based on the risk groups and HSR incidence, it was found that high risk group (HRG) patients were significantly more likely to develop HSR compared to the standart risk group (SRG) and intermediate risk group (MRG) patients (chi-square p = 0.003, CI: 95%; odds ratio: 3.12 and 5.91, respectively). Conclusions: In conclusion, IM administration of L-ASNase causes significantly less HSR to L-ASNase than the IV route. Patients with HRGALL have a higher risk of HSR. Since L-ASNase is still used in many developing countries and there are problems in the supply of Erwinia chrysanthemi ASNase (Erwinia), LASNase can be administered IM to reduce the frequency of HSR.
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    Epidemiologic and microbiologic evaluation of catheter-line bloodstream infection in a pediatric hematopoietic stem cell transplant center
    (2023) Adaklı Aksoy, Başak; Kara, Manolya; Sütçü, Murat; Özbek, Ahmet; Zengin Ersoy, Gizem; Başoğlu Öner, Özlem; Aydoğdu, Selime; Gül, Doruk; Bozkurt, Ceyhun; Fışgın, Tunç
    Background: Children who underwent hematopoietic stem cell transplant (HSCT) are at high risk of developing central-line-associated bloodstream infection (CLABSIs). The present study aimed to identify possible risk factors for mortality by analyzing the clinical and laboratory characteristics of patients diagnosed with CLABSI in our pediatric HSCT unit. Methods: The initial CLABSI episodes of 102 children were analyzed. Medical records of the patients were evaluated by preformed standardized surveys. Univariate analysis and multivariate logistic regression analysis were performed to identify risk factors for mortality. Results: Thirty-five patients (34.3%) were female. The median age was 48 month (3-204). The median time to onset of CLABSI was 19 days (4-150). The Gram-negative/Gram-positive bacteria ratio among the causative agents was 57.8 % to 34.3 %. The mortality rate was 12.6%. The presence of severe neutropenia, initiation of inappropriate empirical antibiotic therapy, the presence of hypotension, persistent bacteremia, pediatric intensive care unit admission, growth of carbapenemase-positive Gram-negative microorganism and multi-drug resistant bacteria were significantly high in the mortality group when compared to survivors. The presence of hypotension, inappropriate empirical antibiotic therapy, and persistent bacteremia were found to be independent risk factors for mortality. Conclusion: Rational use of antibiotics, active surveillance/ screening of patients together with improved infection control practices may reduce the incidence and the consequences of CLABSIs.
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    Hemophilia caregiver burden in a low socioeconomic region of Turkey
    (2023) Zengin Ersoy, Gizem; Ertekin, Mehtap; Dikme, Gürcan
    Objective: This study aims to evaluate the caregiver burden of parents of hemophilia patients and related factors in the southeast region of Turkey, where access to a regular healthcare facility is more complicated than in other areas. Materials and methods: Twenty-six caregivers of patients with hemophilia were consecutively enrolled in this non-interventional study. Caregiver burden is measured using the "HemophiliaAssociated Caregiver Burden Scale" (HEMOCAB). Results: Hemophilia affects 65.4% of caregivers emotionally, and 92.3% feel the burden caused by financial problems related to hemophilia. The perception of the patients by caregivers was negative in the groups of low educational degree and unstable employment status (P = .037 and P = .017, respectively). The employment status and job changes influence the caregiver burden because of hemophilia (P = .034 and P = .001, respectively). The groups of those who spent greater than 5 hours for transportation to the hemophilia treatment center (HTC) had a higher burden (P = .001). Multiple linear regression analysis analyzed variables affecting HEMOCAB, frequency, and burden total scores. The model created with the burden total score was statistically significant (P = .047). Conclusion: The main factors affecting caregiver burden were educational status, working conditions, and economic difficulties, as well as the length of infusion times and transfer to HTCs. There is a need to develop socioeconomic policies related to these problems.
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    Hepatocellular carcinoma in ADA-SCID patient after hematopoietic stem cell transplantation
    (2023) Uçku, Duygu; Armutlu, Ayşe; Çipe, Funda; Zengin Ersoy, Gizem; Karakaya, Afak Durur; Arıkan, Çiğdem
    Adenosine deaminase (ADA) deficiency is one of the most prevalent forms of severe combined immunodeficiency and results in the accumulation of toxic substrates which creates a systemic metabolic disease. It predisposes patients to the development of malignancies, most commonly lymphoma. We report an 8-month-old infant with ADA deficient severe combined immunodeficiency who developed progressive liver dysfunction and hepatocellular carcinoma after successful hematopoietic stem cell transplantation. This is the first case report of an ADA-deficient patient who presented with hepatocellular carcinoma and gives an insight into the complex etiology that can lie behind liver dysfunction in these patients.
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    Neurologic status of patients with purine nucleoside phosphorylase deficiency before and after hematopoetic stem cell transplantation
    (2023) Gemici Karaaslan, Betül; Turan, Işılay; Aydemir, Sezin; Akyüncü Meriç, Zeynep; Atay, Didem; Akçay, Arzu; Ayaz Sarı, Aysun; Hersfield, Michael; Çipe, Funda; Adaklı Aksoy, Başak; Zengin Ersoy, Gizem; Bozkurt, Ceyhun; Kendir Demirkol, Yasemin; Öztürk, Gülyüz; Aydoğmuş, Çiğdem; Kıykım, Ayça; Çokuğraş, Haluk
    Background Purine nucleoside phosphorylase (PNP) defciency is a rare autosomal recessive combined immunodefciency. The phenotype is profound T cell defciency with variable B and NK cell functions and results in recurrent and persistent infections that typically begin in the frst year of life. Neurologic fndings occur in approximately two-thirds of patients. The mechanism of neurologic abnormalities is unclear. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for PNP defciency. Methods We report here six patients from fve unrelated families with PNP defciency treated in two centers in Turkey. We evaluated the neurological status of patients and compared to post-transplantation period if available. Then, we performed PubMed, Google Scholar, and Researchgate searches using the terms “PNP” and “hematopoietic stem cell transplantation” to fnd all reported cases of PNP transplantation and compared to our cohort. Results Six patients were treated in two centers in Turkey. One patient died from post-transplant complications. The other four patients underwent successful HSCT with good immune reconstitution after transplantation (follow-up 21–48 months) and good neurological outcomes. The other patient with a new mutation is still waiting for a matching HLA donor. Discussion In PNP defciency, clinical manifestations are variable, and this disease should be considered in the presence of many diferent clinical fndings. Despite the comorbidities that occurred before transplantation, HSCT currently appears to be the only treatment option for this disease. HSCT not only cures immunologic disorders, but probably also improves or at least stabilizes the neurologic status of patients.
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    Restrictive effects of thalassemia on respiratory functions: One center experience
    (2023) Zengin Ersoy, Gizem; Nain, Ercan; Ertekin, Mehtap; Terzi, Özlem; Şaşıhüseyinoğlu, Ayşe Şenay; Dikme, Gürcan
    Objective: Respiratory functions in thalassemia major (TM) patients concerning poor chelation are a frequently researched issue. Our study aims to evaluate the lung functions of our patients with TM in the chronic transfusion program and to correlate them with their age, ferritin levels, and pre-transfusion hemoglobin values. Methods: Height, weight, pulmonary function test (PFT) results, pre-transfusion hemoglobin levels, and ferritin levels of 97 patients (55 boys and 42 girls) without any underlying cardiac or chronic respiratory disease were recorded. PFT is consisted of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), the ratio of FEV1/FVC to peak expiratory flow (PEF), and forced mid-exhaled flow between 25% and 75% of mid-expiratory flow (MEF25-75). Data were analyzed with IBM SPSS V25. Results: Low FVC was observed in 58 patients (60%), and low FEV1 was observed in 26 patients (27.6%). Low PEF was observed in 62 patients (64.5%), and low MEF25-75 was observed in 8 (8.3%). PFT was affected in 75 patients (78.1%). The pattern of involvement was restrictive. Age, height, and ferritin values significantly affected the MEF25-75 (p<0.05). Age and pre-transfusion hemoglobin values had a significant effect on the FVC test (p<0.05). There was a weak negative correlation between ferritin values and MEF25-75 (r=-0.221) and a weak positive correlation between pre-transfusion hemoglobin and FVC (r=0.222). Conclusion: Age and height are the main risk factors affecting FEV1, MEF25-75, and PEF. Serum ferritin has only an effect on MEF25-75 in our study. The respiratory functions of TM patients were affected in a restrictive pattern.
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    Tandem high-dose chemotherapy followed by autologous stem cell transplantation: An infant with trilateral retinoblastoma
    (2023) Töret, Ersin; Özdemir, Zeynep Canan; Zengin Ersoy, Gizem; Öztunalı, Çiğdem; Bozkurt, Ceyhun; Kebudi, Rejin
    Background: Retinoblastoma (RB) is the most common intraocular malignancy in childhood. Advanced RB, associated with exceedingly poor prognosis, requires more intensive multiagent chemotherapy than conventional regimens. Rescue of the bone marrow after intensive chemotherapy is achieved with stem cell transplantation. The sequential courses (tandem transplantation) of high-dose chemotherapy followed by autologous stem cell transplantation allow for even greater dose intensity in consolidation with the potential to use different active chemotherapeutics at each transplant and have proven feasible and successful in treating children with recurrent/refractory solid tumors. Case description: We report an infant with trilateral high-risk RB who received tandem high-dose chemotherapy (HDC) followed by autologous stem cell transplantation after the conventional chemotherapy. A 5-month-old female patient presented with strabismus, and the ophthalmoscopic examination showed intraocular tumoral lesions in both eyes. Magnetic resonance imaging (MRI) concluded the trilateral retinoblastoma diagnosis due to a tumoral mass in the optic chiasm. The follow-up ophthalmologic examinations and the MRI detected stable disease after six cycles of multiagent chemotherapy. Conclusions: Rescue with autologous stem cell transplantation after HDC allows for an increase in chemotherapy intensity. Tandem transplantation provides the chance to perform different chemotherapeutics at each transplant and enables an increase in the chemotherapy intensity, thus providing a positive effect on disease-free survival.