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Öğe A novel homozygous six base pair deletion found in the NFATC2 gene in a patient with EBV-associated lymphoproliferation(2024) Erman, Baran; Köstel Bal, Sevgi; Aydoğmuş, Çiğdem; Ersoy, Gizem Zengin; Boztuğ, Kaan...Öğe Evaluation of the risk factors for BK virus-associated hemorrhagic cystitis in pediatric bone marrow transplantation patients: Does post-transplantation cyclophosphamide increase the frequency?(2022) Ersoy, Gizem Zengin; Bozkurt, Ceyhun; Aksoy, Başak Adaklı; Öner, Özlem Başoğlu; Aydoğdu, Selime; Çipe, Funda; Sütçü, Murat; Özkaya, Ozan; Fışgın, TunçBackground: BKV-HC is one of the most significant complications of HSCT. This ret -rospective study aimed to determine the frequency of BKV-HC in pediatric patients undergoing HSCT, detect the associated risk factors for the development of BKV-HC, and explore the effects of post-transplantation Cy use.Methods: Three hundred twenty-seven patients (girls: 121, boys: 206) were analyzed according to sex, conditioning regimen, transplantation type, donor relatedness, stem cell source, the presence and grade of aGVHD, CMV co-existence, and Cy use.Results: Multivariate analysis confirmed the prognostic importance of age (OR: 4.865), TBI use, the presence of aGVHD (OR: 2.794), CMV coinfection (OR: 2.261), and Cy use (OR: 27.353). A statistically significant difference was found between the mean BKV-HC follow-up times compared with post-transplantation Cy intake (p< .001). The BKV-HC rate increased as the number of risk factors of the patient increased.Conclusion: BKV-HC is an essential complication of HSCT primarily associated with Cy use, the presence of aGVHD, and donor relatedness. The present study shows that the use of Cy in the post-transplantation period further increases BKV-HC risk in pediatric patients, regardless of dose.Öğe Factors associated with the development of adrenal insufficiency in patients with juvenile idiopathic arthritis who received systemic corticosteroids(2023) Ersoy, Gizem Zengin; Ergüven, Müferet; Yıldız, MetinAim: In juvenile idiopathic arthritis (JIA), systemic corticosteroids are reserved for cases with serious organ involvement, those with macrophage activation syndrome, and in the presence of high disease activity in oligoarticular and polyarticular JIA. However, systemic steroids may lead to serious side effects linked to adrenal insufficiency (AI). This study aimed to investigate factors related to AI in children with JIA who received systemic steroids.Materials and Methods: Twenty-five children with AI (serum cortisol <18 mu g/dL 30 minutes after adrenocorticotropic hormon stimulation) and 25 children without AI were included in this study. The subjects' characteristics, type of JIA, arthritis location, laboratory measurements, and number of joints involved were recorded. The type of glucocorticoid administered, the treatment protocol, and the cumulative steroid dose were recorded. The primary endpoint was the difference in clinical characteristics, laboratory measurements and systemic corticosteroid dose in those children with or without AI.Results: The median cumulative steroid dose was significantly higher in those patients with AI compared to those without [2,500 (1,370-4,400) mg vs. 963 (650-2,500) mg, p=0.010]. Patients with oligoarticular JIA had a 6.7-fold lower risk of AI compared to those with other JIA types [odds ratio (OR): 0.149, 95% confidence interval (CI): 0.035-0.643, p=0.011]. Those patients with higher cumulative steroid doses (>1,000 mg) had a 7.5-fold higher risk of AI than those with lower doses (OR: 7,500, 95% CI: 1,634-34,416, p=0.010). Conclusion: Our findings show that non-oligoarticular JIA and high cumulative steroid doses are predictive for AI development in this patient subset; thus, systemic corticosteroids should be reserved for more aggressive JIA types and the cumulative dose should be limited to 1,000 mg.Öğe Outcomes of hematopoietic stem cell transplantation in patients with thalassemia major: how do anti-HLA antibodies impact?(Wiley, 2024) Ersoy, Gizem Zengin; Aksoy, Başak Adaklı; Erdem, Melek; Karataş, Lokman; Aydoğdu, Selime; Öner, Özlem Başoğlu; Dikme, Guercan; Bozkurt, Ceyhun; Fışgın, TunçAimTo investigate the effects of anti-human Leucocyte Antigen (HLA) antibody positivity on early hematopoietic stem cell transplantation (HSCT) results in patients with thalassemia major (TM).MethodsOne hundred and twenty-four HLA-matched HSCTs were performed in patients with TM between 2015 and 2022. Ninety-one patients were screened for anti-HLA antibodies by testing panel reactive antigens (PRA). Demographic and transplantation characteristics of patients were recorded. The presence of PRA was tested with the Antibody Testing Assay (Luminex LIFECODES HLA Antibody Identification System).ResultsThe number of PRA-positive patients was 54. There was no relationship between acute graft versus host disease (GVHD), chronic GVHD, grade of GVHD, and viral reactivation of the patients. However, platelet engraftment took around 3 days longer in the PRA-positive group (p = 0.05). The median number of erythrocyte transfusions was significantly higher in PRA-positive patients in the post-transplant period (p = 0.003), as was the median number of platelet transfusions (p = 0.003). Treosulfan conditioning increased the stable mixed chimerism (MC) rate by 3.8-fold (p = 0.011). In contrast, reduced rates of MC were found in patients who received matched unrelated donor cells or peripherally derived stem cells (p = 0.011 and p = 0.039, respectively) in the posttransplantation period in TM patients. PRA-positivity did not affect MC (p = 0.478). However, 80% of patients who had primary graft failure (n = 5; p = 0.59) and 75% of patients who died (n = 4) were PRA positive (p = 0.64), but these results were statistically insignificant due to the low number of patients.ConclusionAnti-HLA antibodies primarily delayed platelet engraftment in TM patients and increased the erythrocyte and thrombocyte transfusion requirements. Although PRA positivity was more common in patients with primary graft failure or who died, there was no statistically significant impact of PRA positivity on chimerism, acute or chronic GVHD, viral activation, or mortality rates.Öğe Outcomes of hematopoietic stem cell transplantation in patients with thalassemia major: how do anti-HLA antibodies impact?: the impact of anti-HLA antibodies on transplantation outcomes in thalassemia major(2024) Ersoy, Gizem Zengin; Aksoy, Başak Adaklı; Erdem, Melek; Karataş, Lokman; Aydoğdu, Selime; Başoğlu Öner, Özlem; Dikme, Gürcan; Bozkurt, Ceyhun; Fışgın, TunçAim: To investigate the effects of anti-human Leucocyte Antigen (HLA) antibody positivity on early hematopoietic stem cell transplantation (HSCT) results in patients with thalassemia major (TM). Methods: One hundred and twenty-four HLA-matched HSCTs were performed in patients with TM between 2015 and 2022. Ninety-one patients were screened for anti-HLA antibodies by testing panel reactive antigens (PRA). Demographic and transplantation characteristics of patients were recorded. The presence of PRA was tested with the Antibody Testing Assay (Luminex LIFECODES HLA Antibody Identification System). Results: The number of PRA-positive patients was 54. There was no relationship between acute graft versus host disease (GVHD), chronic GVHD, grade of GVHD, and viral reactivation of the patients. However, platelet engraftment took around 3 days longer in the PRA-positive group (p = 0.05). The median number of erythrocyte transfusions was significantly higher in PRA-positive patients in the post-transplant period (p = 0.003), as was the median number of platelet transfusions (p = 0.003). Treosulfan conditioning increased the stable mixed chimerism (MC) rate by 3.8-fold (p = 0.011). In contrast, reduced rates of MC were found in patients who received matched unrelated donor cells or peripherally derived stem cells (p = 0.011 and p = 0.039, respectively) in the posttransplantation period in TM patients. PRA-positivity did not affect MC (p = 0.478). However, 80% of patients who had primary graft failure (n = 5; p = 0.59) and 75% of patients who died (n = 4) were PRA positive (p = 0.64), but these results were statistically insignificant due to the low number of patients. Conclusion: Anti-HLA antibodies primarily delayed platelet engraftment in TM patients and increased the erythrocyte and thrombocyte transfusion requirements. Although PRA positivity was more common in patients with primary graft failure or who died, there was no statistically significant impact of PRA positivity on chimerism, acute or chronic GVHD, viral activation, or mortality rates.Öğe Outcomes of HLA-mismatched HSCT with TCR?ß/CD19 depletion or post-HSCT cyclophosphamide for inborn errors of immunity(2024) Lum, Su Han; Albert, Michael H.; Gilbert, Patrick; Sirait, Tiarlan; Algeri, Mattia; Muratori, Rafaella; Fournier, Benjamin; Laberko, Alexandra; Karakükcü, Musa; Ünal, Ekrem; Ayas, Mouhab F.; Yadav, Satya Prakash; Fışgın, Tunç; Elfeky, Reem; Fernandes, Juliana Folloni; Faraci, Maura; Cole, Theresa; Schulz, Ansgar S.; Meisel, Roland; Zecca, Marco; Ifversen, Marienne; Biffi, Alessandra; Diana, Jean-Sebastien; Vallee, Tanja C.; Giardino, Stefano; Ersoy, Gizem Zengin; Moshous, Despina; Gennery, Andrew R.; Balashov, Dmitry; Bonfim Carmem M. S.; Locatelli, Franco; Lankester, Arjan C.; Neven, Benedicte; Slatter, Mary A.HLA-mismatched transplants with either in vitro depletion of CD3+TCRαβ/CD19 (TCRαβ) cells or in vivo T-cell depletion using post-transplant cyclophosphamide (PTCY) have been increasingly used for patients with inborn errors of immunity (IEI). We performed a retrospective multicenter study via the EBMT registry on 306 children with IEI undergoing first transplant between 2010-2019 from an HLA-mismatched donor using TCRαβ (n=167) or PTCY (n=139). Median age at HSCT was 1.2 years (range, 0.03-19.6 years). The 3-year overall survival (OS) was 78% (95% confidence interval (CI), 71-84%) after TCRαβ and 66% (57-74%) after PTCY (p=0.013). Pre-HSCT morbidity score (hazard ratio (HR) 2.27, 1.07-4.80, p=0.032) and non-Busulfan/Treosulfan conditioning (HR 3.12, 1.98-4.92, p<0.001) were the only independent predictors of unfavorable OS. The 3-year event-free survival (EFS) was 58% (50-66%) after TCRαβ and 57% (48-66%) after PTCY (p=0.804). Cumulative incidence of severe acute GvHD was higher after PTCY (15%, 9-21%) than TCRαβ (6%, 2-9%, p=0.007), with no difference in chronic GvHD (PTCY, 11%, 6-17%; TCRαβ, 7%, 3-11%, p=0.173). The 3-year GvHD-free EFS was 53% (44-61%) after TCRαβ and 41% (32-50%) after PTCY (p=0.080). PTCY had significantly higher rates of veno-occlusive disease (14.4% versus TCRαβ 4.9%, p=0.009), acute kidney injury (12.7% versus 4.6%, p=0.032) and pulmonary complications (38.2% versus 24.1%, p=0.017). Adenoviraemia (18.3% versus PTCY 8.0%, p=0.015), primary graft failure (10%, versus 5%, p=0.048), and second HSCT (17.4% versus 7.9%, p=0.023) were significantly higher in TCRαβ. In conclusion, this study demonstrates that both approaches are suitable options in IEI patients, although characterized by different advantages and outcomes.Öğe The effect of biofilm inhibitor N-acetylcysteine on the minimum inhibitory concentration of antibiotics used in Gram-negative bacteria in the biofilm developed on catheters(2022) Aksoy, Nilay; Vatansever, Cansu; Ersoy, Gizem Zengin; Aksoy, Başak Adaklı; Fışgın, TunçThe study determined the effect of N-acetylcysteine (NAC) on the susceptibility of various antibiotics used to treat Gram-negative catheter-related infection in isolates obtained from pediatric patients admitted to the hematology and oncology department of Medical Park Bahçelievler hospital in Istanbul, Turkey. Biofilms were created in vitro utilizing clinical isolates of Escherichia coli, Pseudomonas aeruginosa, Pseudomonas putida, and Proteus mirabilis. 24 h old biofilms were developed on 96-well plate with strains and the minimum biofilm inhibitory concentration (MBIC) of six antibiotics were measured before and after the addition of 75 mg/ml N-acetylcysteine with microplate reader at 450 nm after crystal violet assay. The addition of NAC reduce the MBIC of cefepime, ceftazidime, colistin, meropenem from (16, 16, 8, 4 μg/ml) to (8, 4, 4, 2 μg/ml) respectively in E. coli (isolate 1). In P. aeruginosa (isolate 4), the MBIC of amikacin, ceftazidime, meropenem (64, 32, and 32 μg/ml) reduced to (8, 1, and 0.5 μg/ml) respectively. MBIC of cefepime, colistin, meropenem (32, 16,and 16 μg/ml) reduced to (2, 2,and 0.5 μg/ml) respectively in P. putida (isolate 5). In P. mirabilis (isolate 6), MBIC of amikacin, cefepime, ceftazidime, colisitin and meropenem (64, 128, 32, 4, and 32 μg/ml) reduced to (8, 8, 1, 1, 4 μg/ml). NAC in combination therapy can practically reduce the MBIC of antibiotics used to treat Gram negative bacteria that develop biofilm in medical catheters. As a result, these combinations can be considered as an essential alternative for increasing the antibiotic susceptibility of pathogenic microorganisms and thus increasing treatment success rates.Öğe The impact of Treosulfan-based conditioning for inborn errors of immunity: Is dose monitoring crucial?(2023) Ersoy, Gizem Zengin; Çipe, Funda; Fışgın, Tunç; Adaklı Aksoy, Başak; Başoğlu Öner, Özlem; Hashemi, Nazlı; Aydoğdu, Selime; Erdem, Melek; Dikme, Gürcan; Murat, Koza; Bozkurt, CeyhunIntroduction: In children with inborn errors of immunity (IEI) who will receive a hematopoietic stem cell transplant (HSCT) treosulfan-based conditioning is currently preferred. The aim of this study was to investigate early and late outcomes in pediatric IEI patients receiving pre-HSCT treosulfan and to examine the effect of treosulfan dose monitoring on outcomes. Methods: Seventy-three pediatric patients receiving this management between 2015 and 2022 were included. Results: Overall survival rate was 80%, and event-free survival was 67.8%. A larger treosulfan dose AUC after first application increased the rate of early toxicity (p = .034) and slowed lymphocyte engraftment (r = .290; p = .030). Underlying disease, treosulfan AUC, donor type, stem cell type, number of immunosuppressive agents, the dose of anti-thymocyte globulin, and post-transplantation cyclophosphamide did not to increase risk of acute graft-versus-host disease. The risk of mixed chimerism (MC) in patients with autoimmune lymphoproliferative syndrome and leukocyte adhesion deficiency were higher than those with severe combined immunodeficiency (p = .021 and p = .014, respectively). The risk of MC was lower in those receiving peripheral blood stem cells (SC) compared with bone marrow derived SC (OR = .204, p = .022). Conclusion: The AUC of the treosulfan dose was not associated with poorer late outcomes. Treosulfan is an agent that can be used safely in the IEI patient group, level measurement appears essential to identify early toxicities. Prospective studies with more extended follow-up periods are needed.Öğe The impact of treosulfan-based conditioning for primary immune deficiencies : single center experience(2023) Ersoy, Gizem Zengin; Çipe, Funda; Aksoy, Başak Adaklı; Hashemi, Nazlı; Öner, Özlem Başoğlu; Aydoğdu, Selime; Dikme, Gürcan; Erdem, Melek; Bozkurt, Ceyhun; Fışgın, Tunç...Öğe Would monitorizing treosulfan levels in patients transplanted for transfusion dependent thalassemia be beneficial in terms of chimerizm? a single center experience(2023) Aksoy, Başak Adaklı; Ersoy, Gizem Zengin; Elsayed, Mariam; Öner, Özlem Başoğlu; Aydoğdu, Selime; Dikme, Gürcan; Erdem, Melek; Fışgın, Tunç; Bozkurt, Ceyhun...
