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Öğe A Case of Gonadotropin-independent precocious puberty due to germ cell tumor in the frontal lobe(Karger, 2019) Hacıhamdioğlu, Bülent; Yalçın, Koray; Çelen, Safiye Suna; Hazar, VolkanIt is known that gonadotropin-independent or peripheral precocious puberty (PPP) may develop due to tumors that secrete beta human chorionic gonadotropin (Beta-HCG)Öğe COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group(Wiley, 2024) Bozkurt, Ceyhun; Hazar, Volkan; Malbora, Baris; Kupesiz, Alphan; Aygunes, Utku; Fisgin, Tunc; Karakukcu, MusaBackgroundData on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited.ObjectivesThe study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection.MethodIn this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022.ResultsThe median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality.ConclusionWhile COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD. COVID-19 in children following HSCT is frequently asymptomatic/mild. Nonetheless, 12% of patients have such severe disease that they need intensive care. Adverse outcomes are expected in mismatched HSCT, lymphopenia, LRTD, and MIS-C.imageÖğe Different kinetics and risk factors for isolated extramedullary relapse after allogeneic hematopoietic stem cell transplantation in children with acute leukemia(Elsevier, 2021) Hazar, Volkan; Öztürk, Gülyüz; Yalçın, Koray; Uygun, Vedat; Aksoylar, Serap; Bozkurt, CeyhunRelapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most frequent cause of posttransplant mortality. Isolated extramedullary relapse (iEMR) after HSCT is relatively rare and not well characterized, particularly in pediatric patients. We retrospectively analyzed 1527 consecutive pediatric patients with acute leukemia after allo-HSCT to study the incidence, risk factors and outcome of iEMR compared to systemic relapse. The 5-year cumulative incidence of systemic relapse ?either bone morrow (BM) only or combined with EMR? and iEMR was 24.8% and 5.5%, respectively. The onset of relapse after allo-HSCT was significantly longer in EM sites than in BM sites (7.19 and 5.58 months, respectively; p: 0.013). CR2+/active disease at transplantation (HR, 3.1, p<0001) and prior extramedullary disease (HR, 2.3; p: 0.007) were independent risk factors for iEMR. Chronic graft-versus-host disease (GVHD) reduced the risk of systemic relapse (HR, 0.5; p: 0.043) but did not protect against iEMR. The prognosis of patients who developed iEMR remained poor but was slightly better than that of patients who developed systemic relapse (3-year overall survival, 16.5% vs 15.3%, p: 0.089). Patients experiencing their first systemic relapse continued to have further systemic relapse, but only a minority progressed to iEMR, while those experiencing their iEMR at first relapse developed further systemic and isolated extramedullary relapses with approximately similar frequencies. Second iEMR was more common after the first iEMR than after the first systemic relapse (58.8% vs 13.0%, p: 0.001) and was associated with a poor outcome. iEMR has a poor prognosis, particularly after the 2nd relapse, and effective strategies are needed to improve outcomes.Öğe Hematopoetic stem cell transplantation in CD40 ligand deficiency(SPRINGERNATURE, 2020) Uygun, Vedat; Uygun, Dilara Fatma Kocacık; Daloğlu, Hayriye; Öztürkmen, Seda; Kılıç, Suar Çakı; Bingöl, Aysen; Yalçın, Koray; Çelen, Safiye Suna; Hazar, Volkan; Tezcan Karasu, Gülsun; Yeşilipek, Akif[No Abstract Available]Öğe Hematopoietic stem cell transplantation in CD40 ligand deficiency: a single-center experience(Wiley, 2020) Uygun, Dilara Fatma Kocacık; Uygun, Vedat; Tezcan Karasu, Gülsun; Daloğlu, Hayriye; Öztürkmen, Seda Irmak; Çelmeli, Fatih; Torun, Selda Hançerli; Özen, Ahmet; Barış, Safa; Aydıner, Elif Karakoç; Yalçın, Koray; Kılıç, Suar Çaki; Hazar, Volkan; Bingöl, Aysen; Yeşilipek, AkifDeficiency of the CD40L, expressed on the surface of T lymphocytes, is caused by mutations in the glycoproteinCD40L (CD154)gene. Resulting defective humoral and cellular responses cause a clinical presentation that includes recurrent sinopulmonary bacterial infections, opportunistic infections, sclerosing cholangitis, neutropenia, and autoimmune manifestations. HSCT represents the only curative treatment modality. However, the therapeutic decision to use HSCT proves challenging in many cases, mainly due to the lack of a phenotype-genotype correlation. We retrospectively reviewed patients with CD40L deficiency who were transplanted in Antalya and Goztepe MedicalPark Pediatric HSCT units from 2014 to 2019 and followed by Akdeniz University School of Medicine Department of Pediatric Immunology. The records of eight male cases, including one set of twins, were evaluated retrospectively. As two transplants each were performed on the twins, a total of ten transplants were evaluated. Conditioning regimens were predominantly based on myeloablative protocols, except for the twins, who received a non-myeloablative regimen for their first transplantation. Median neutrophil and platelet engraftment days were 13 (range 10-19) and 14 (range 10-42) days, respectively. In seven of ten transplants, a CMV reactivation was developed without morbidity. None of the patients developed GVHD, except for one mild case of acute GVHD. All patients survived, and the median follow-up was 852 days. Our data show that HSCT for patients with CD40 ligand deficiency is a potentially effective treatment for long-term disease control.Öğe Impact of Replacing Low Dose Cyclophosphamide with Fludarabine in Children with Acute Myeloid Leukemia Undergoing Transplantation During First Complete Remission(Akad Doktorlar Yayinevi, 2023) Uygun, Vedat; Karasu, Gulsun; Yalcin, Koray; Ozturkmen, Seda; Daloglu, Hayriye; Celen, Safiye Suna; Hazar, VolkanBusulfan (BU)-based myeloablative conditioning is a standard conditioning regimen for children with AML; however, it is not clear yet which combination of cyclophosphamide (CY) and fludarabine (FLU) is most effective. We performed a study to compare the results of BUCY120 and BU-FLU in pediatric patients with AML in CR1 undergoing allo-HSCT from matched sibling donors. With the combination of BU, 15 patients were given 120 mg/kg of CY, and 12 patients were given 150 mg/m2 of FLU, respectively, in the condition regimen. Patients treated with BUFLU relapsed less than those treated with BUCY120 (p= 0.03). Moreover, these patients engrafted platelets earlier than the BUCY120 administered patients (p= 0.03). The frequency of complications in both groups was comparable. There was no significant difference in survival analysis between the groups. BUFLU has a low toxicity profile, making it a reasonable choice for children with AML in CR1 with low risk and a lower relapse frequency compared to BUCY120.Öğe Prognostic factors for survival in children who relapsed after allogeneic hematopoietic stem cell transplantation for acute leukemia(2020) Hazar, Volkan; Tezcan Karasu, Gülsün; Öztürk, Gülyüz; Küpesiz, Alphan; Aksoylar, Serap; Özbek, Namık; Uygun, Vedat; İleri, Talia; Okur, Fatma Visal; Koçak, Ülker; Çakı Kılıç, Suar; Akçay, Arzu; Güler, Elif; Kansoy, Savaş; Karakükcü, Musa; Bayram, İbrahim; Aksu , Tekin; Yeşilipek, Akif; Karagün, Barbaros Şahin; Yılmaz, Şebnem; Ertem, Mehmet; Uçkan, Duygu; Fışgın, Tunç; Gürsel, Orhan; Yaman, Yöntem; Bozkurt, Ceyhun; Gökçe, MügeBackground: Post-transplant relapse has a dismal prognosis in children with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Data on risk factors, treatment options, and outcomes are limited. Procedure: In this retrospective multicenter study in which a questionnaire was sent to all pediatric transplant centers reporting relapse after allo-HSCT for a cohort of 938 children with acute leukemia, we analyzed 255 children with relapse of acute leukemia after their first allo-HSCT. Results: The median interval from transplantation to relapse was 180 days, and the median follow-up from relapse to the last follow-up was 1844 days. The 3-year overall survival (OS) rate was 12.0%. The main cause of death was disease progression or subsequent relapse (82.6%). The majority of children received salvage treatment with curative intent without a second HSCT (67.8%), 22.0% of children underwent a second allo-HSCT, and 10.2% received palliative therapy. Isolated extramedullary relapse (hazard ratio (HR): 0.607, P = .011) and relapse earlier than 365 days post-transplantation (HR: 2.101, P < .001 for 0-180 days; HR: 1.522, P = .041 for 181-365 days) were found in multivariate analysis to be significant prognostic factors for outcome. The type of salvage therapy in chemosensitive relapse was identified as a significant prognostic factor for OS. Conclusion: A salvage approach with curative intent may be considered for patients with post-transplant relapse, even if they relapse in the first year post-transplantation. For sustainable remission, a second allo-HSCT may be recommended for patients who achieve complete remission after reinduction treatment.Öğe Ruxolitinib salvage therapy is effective for steroid-refractory graft-versus-host disease in children: a single-center experience(Wiley, 2020) Uygun, Vedat; Tezcan Karasu, Gülsün; Daloğlu, Hayriye; Öztürkmen, Seda; Kılıç, Suar Çakı; Yalçın, Koray; Çelen, Safiye Suna; Hazar, Volkan; Yeşilipek, AkifBackground Despite the increasing performance of allogeneic hematopoietic cell transplantation over the last decades, graft-versus-host disease (GVHD) remains the main cause of morbidity and mortality. The efficacy of ruxolitinib against GVHD has been demonstrated in adult studies; however, very few studies have been conducted in children. Procedure This study aimed to evaluate the efficacy of ruxolitinib in 29 children with steroid-refractory acute or chronic GVHD. Twenty-five (87%) patients received at least three different immune modulator agents, including methylprednisolone, before initiating ruxolitinib. Results All grade 2 acute GVHD patients completely responded to ruxolitinib treatment; 82% of high-grade (3-4) acute GVHD patients and 80% of chronic GVHD (moderate-severe) patients had at least a partial response. Of seven patients with bronchiolitis obliterans, five had a partial response after ruxolitinib. Of 29 patients, 22 were administered steroids at any time in the first month of acute GVHD or the first three months of chronic GVHD during ruxolitinib usage, which was significantly tapered by the end of the observation period. Conclusion Steroid-refractory acute and chronic pediatric GVHD patients treated with ruxolitinib had a high overall response rate, with the additional benefit of steroid sparing.Öğe Timing of initiation of calcineurin inhibitors in pediatric haploidentical transplantation with post-transplantation cyclophosphamide: Effects on survival, relapse, and cytokine release syndrome(Karger, 2022) Uygun, Vedat; Karasu, Gülsüm; Yalçın, Koray; Öztürkmen, Seda; Daloğlu, Hayriye; Çelen, Safiye Suna; Hazar, Volkan; Yeşilipek, AkifBackground: The use of unmanipulated haploidentical hematopoietic stem cell transplantations (haplo-HSCT) with post-transplant cyclophosphamide (PTCY) in children has emerged as an acceptable alternative to the patients without a matched donor. However, the timing of calcineurin inhibitors (CNIs) used in combination with PTCY is increasingly becoming a topic of controversy. Method: We evaluated 49 children with acute leukemia who underwent unmanipulated haplo-HSCT with PTCY according to the initiation day of CNIs (pre- or post-cyclophosphamide [CY]). Results: There were no significant differences in the overall survival analysis between the 2 groups. The cumulative incidence of relapse at 2 years was 21.2% in the pre-CY group and 38.9% in the post-CY group (p = 0.33). Cytokine release syndrome (CRS) was observed more frequently in the post-CY group (p = 0.04). The overall survival and event-free survival at 2 years in patients with and without CRS in the pre-CY group were 42.9% versus 87.5% (p = 0.04) and 38.1% versus 87.5% (p = 0.04), respectively. Conclusion: Our study shows that the argument for starting CNI administration after CY is tenuous, and the rationale for not starting CNIs before CY needs to be reconsidered.
