Publications by authors named "Serap Aksoylar"

44 Publications

Metabolic syndrome and risk factors after hematopoietic stem cell transplantation in children and adolescents.

J Pediatr Endocrinol Metab 2021 Apr 25;34(4):485-493. Epub 2021 Feb 25.

Department of Pediatric Hematology & Oncology and Bone Marrow Transplantation, Medical School of Ege University, Izmir, Turkey.

Objectives: The early and late complications after hematopoietic stem cell transplantation (HSCT) determine the patients' prognosis and life quality. We aim to determine the metabolic syndrome development frequency after HSCT in children to find out the risk factors and compare them with healthy adolescents.

Methods: Thirty-six children who underwent HSCT at least two years ago were analyzed prospectively and cross-sectionally. Our study included 18 healthy children between the ages of 11 and 17 as a control group. All of the cases were assessed in terms of metabolic syndrome (MS) through the use of Modified WHO Criteria.

Results: The patients' median age was 10.6 (5.1-17) years, the median time of follow-up after HCST was 4.1 (2-13.5) years and 70% were male. Two cases were diagnosed with MS (5.6%). When considered in terms of the sub-components of MS, 2 cases (5.6%) were found to have obesity, 17 cases (47%) abnormal glucose tolerance, 11 cases (30.7%) dyslipidemia, and 3 cases (8.6%) hypertension. The MS rate was not different when compared with the 11-17 year-old healthy control group (0 vs. 11%, p=0.48). Myeloablative conditioning regimen (65 vs. 20%) and the increased age at which HSCT was performed were considered to be risk factors in terms of insulin resistance (p=0.025 and 0.002).

Conclusions: Age and conditioning regimens were found to be the risk factors for insulin resistance development. The long-term follow-up of the cases who had undergone HSCT in childhood in terms of MS and its sub-components is important in order to increase life quality.
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http://dx.doi.org/10.1515/jpem-2020-0584DOI Listing
April 2021

Prognostic factors for survival in children who relapsed after allogeneic hematopoietic stem cell transplantation for acute leukemia.

Pediatr Transplant 2020 Dec 15:e13942. Epub 2020 Dec 15.

Pediatric BMT Unit, GOP Hospital, Yüzüncü Yıl University Faculty of Medicine, Istanbul, Turkey.

Background: 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.
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http://dx.doi.org/10.1111/petr.13942DOI Listing
December 2020

Hematopoietic cell transplantation in chronic granulomatous disease: a study of 712 children and adults.

Blood 2020 09;136(10):1201-1211

Department of Paediatric Immunology, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.

Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting in life-threatening infections and inflammatory complications. Allogeneic hematopoietic cell transplantation (allo-HCT) can cure the disease, but the indication to transplant remains controversial. We performed a retrospective multicenter study of 712 patients with CGD who underwent allo-HCT transplantation from March 1993 through December 2018. We studied 635 children (aged <18 years) and 77 adults. Median follow-up was 45 months. Median age at transplantation was 7 years (range, 0.1-48.6). Kaplan-Meier estimates of overall survival (OS) and event-free survival (EFS) at 3 years were 85.7% and 75.8%, respectively. In multivariate analysis, older age was associated with reduced survival and increased chronic graft-versus-host disease. Nevertheless, OS and EFS at 3 years for patients ≥18 years were 76% and 69%, respectively. Use of 1-antigen-mismatched donors was associated with reduced OS and EFS . No significant difference was found in OS, but a significantly reduced EFS was noted in the small group of patients who received a transplant from a donor with a >1 antigen mismatch. Choice of conditioning regimen did not influence OS or EFS. In summary, we report an excellent outcome after allo-HCT in CGD, with low incidence of graft failure and mortality in all ages. Older patients and recipients of 1-antigen-mismatched grafts had a less favorable outcome. Transplantation should be strongly considered at a younger age and particularly in the presence of a well-matched donor.
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http://dx.doi.org/10.1182/blood.2020005590DOI Listing
September 2020

Role of a second transplantation for children with acute leukemia following posttransplantation relapse: a study by the Turkish Bone Marrow Transplantation Study Group.

Leuk Lymphoma 2020 06 8;61(6):1465-1474. Epub 2020 Feb 8.

Pediatric BMT Unit, Ege University Faculty of Medicine, Izmir, Turkey.

We examined outcomes of 51 pediatric patients with relapsed acute leukemia (AL) who underwent a second allogeneic hematopoietic stem cell transplantation (alloHSCT). After a median follow-up of 941 days (range, 69-2842 days), leukemia-free survival (LFS) and overall survival (OS) at 3 years were 26.6% and 25.6%, respectively. The nonrelapse mortality rate (NMR) and cumulative incidence of relapse (CIR) were 36.4% and 42.4%, respectively. The Cox regression analysis demonstrated that the risk factors at second transplantation for predicting limited LFS were active disease (hazard ratio (HR) = 5.1), reduced intensity conditioning (RIC) (HR = 5.0), matched unrelated donor (MUD) (HR = 3.4) and performance score <80 (HR = 3.2). Pediatric patients with AL who relapsed after their first alloHSCT may survive with a second alloHSCT. Disease status, conditioning intensity, donor type, and performance score at the second transplantation are the relevant risk factors. A score based on these factors may predict the results of the second transplantation.
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http://dx.doi.org/10.1080/10428194.2020.1716220DOI Listing
June 2020

Intestinal Protozoan Parasitic Infections in Immunocompromised Child Patients with Diarrhea.

Jpn J Infect Dis 2020 May 25;73(3):187-192. Epub 2019 Dec 25.

Department of Parasitology, Ege University Medical School.

Intestinal protozoan parasites are common causes of infectious diarrhea in children receiving anticancer therapy or undergoing transplantation. Additionally, immunosuppression therapy in such patients may exacerbate the symptoms related to these parasitic infections. The aim of this study was to evaluate the prevalence and diagnostic importance of parasitic protozoan infections in children treated for malignancies or undergoing transplantation, and to highlight the control of intestinal parasitic infections for immunosuppressed patients at a hospital in İzmir, Turkey. In total, 82 stool samples from 62 patients were analyzed by microscopic examination and polymerase chain reaction (PCR) for the presence of coccidian parasites. Our results showed that Cryptosporidium, Cyclospora, and Cystoisospora were present in 22.5% (14/62), 9.6% (6/62), and 3.2% (2/62) of the cases using either method, respectively. The prevalence of these coccidian parasites identified with both methods was 35.4% (20/62). Other intestinal parasites (Blastocystis, Giardia, and Entamoeba coli) were detected in 10 patients. PCR analysis showed the presence of all coccidian parasites in the same stool sample for one patient. Finally, both PCR and microscopic examination of the stools revealed that there is a higher prevalence of Cryptosporidium, Cyclospora, and Cystoisospora in immunocompromised children. These examinations allowed an early start of appropriate antibiotic treatments and led to an increased percentage of correctly treated patients.
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http://dx.doi.org/10.7883/yoken.JJID.2019.054DOI Listing
May 2020

Clinical Features and HSCT Outcome for SCID in Turkey.

J Clin Immunol 2019 04 28;39(3):316-323. Epub 2019 Mar 28.

Department of Pediatric Immunology, Hacettepe University Medical School, Ankara, Turkey.

Severe combined immunodeficiency (SCID) is the most serious PID, characterized by T cell lymphopenia and lack of antigen-specific T cell and B cell immune responses, inevitably leading to death within the first year of life if hematopoietic stem cell transplantation (HSCT) is not performed.

Purpose And Methods: Since SCID is a common type of PID with an estimated incidence of 1/10.000 in Turkey, a retrospective analysis of HSCT characteristics, survival, immune recovery, and the major clinical features of SCID prior to HSCT is the aim of this multi-transplant center-based analysis.

Results: A total of 234 SCID patients transplanted between the years 1994 and 2014 were included in the study. Median age at diagnosis was 5 months, at transplantation, 7 months, B- phenotype and RAGs were the most common defects among others. Immune phenotype did not seem to have an effect on survival rate (p > 0.05), Immunoglobulin (Ig) requirement following HSCT did not differ between B+ and B- phenotypes (p > 0.05). Overall survival rate was 65.7% over a period of 20 years. It increased from 54% (1994-2004) to 69% (p = 0.052) during the last 10 years (2005-2014). Ten-year survival after HSCT has improved over time although the difference was not significant. Infection at the time of transplantation (p = 0.006), mismatched related donor (MMRD) (haploidentical parents), and matched unrelated donor (MUD) donor transplants p < 0.001 were the most important factors, significantly affecting the outcome.

Conclusions: This is the first multicenter study with the largest data obtained from transplanted SCID patients in Turkey. Early diagnosis with newborn screening (NBS) together with emerging referrals, treatment by transplantation centers, and specialized teams are mandatory in countries with high parental consanguinity such as Turkey.
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http://dx.doi.org/10.1007/s10875-019-00610-xDOI Listing
April 2019

Long-term Dental Anomalies after Pediatric Cancer Treatment in Children

Turk J Haematol 2019 08 16;36(3):155-161. Epub 2018 Oct 16.

Dokuz Eylül University, Institute of Oncology, Department of Pediatric Oncology, İzmir, Turkey

Objective: The aim of this study is to determine the frequency of dental anomalies (DAs) (microdontia, hypodontia, hyperdontia, enamel defect, root malformation) in pediatric cancer patients at the ages <5 years and between 5 and 7 years, and understand their relationship with the received therapy.

Materials And Methods: Pediatric patients who were diagnosed with cancer and treated before the age of 7 years were investigated in a case- control design. The study included 93 pediatric patients whose ages at diagnosis were between 9 months and 7 years and whose treatments were completed before 5-8 years. Group A consisted of patients in the age range of 9 months to 4 years and Group B consisted of patients in the age range of 5-7 years. Seventy-two siblings with compatible dental age ranges were included in the control group. For both groups, intraoral examinations were performed and panoramic radiographs were taken.

Results: Among the 93 pediatric patients, the mean age was 9.54±1.25 (range: 8-13 years) and 48 (51.6%) patients were male. The most common diagnosis was hematologic malignancy with a rate of 65.5%. At least one DA was detected in 7 (9.7%) individuals of the control group and in 78 (83.9%) of the patient group. While the patients in the study group had all kinds of DAs, those in the control group had only enamel defects. The rates of microdontia (p=0.077) and hypodontia (p=0.058) were detected to be significantly higher in Group A than in Group B. Root malformation was more common in patients receiving chemotherapy and radiotherapy than in those receiving only chemotherapy (p=0.006).

Conclusion: In this study it was found that the pediatric patients who received cancer treatment before the age of 7 years constituted a high-risk group for DAs. The frequencies of microdontia and hypodontia were increased even more when the patient was treated for cancer before 5 years of age.
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http://dx.doi.org/10.4274/tjh.galenos.2018.2018.0248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682778PMC
August 2019

A Case of Allergic Broncopulmonary Aspergillosis Associated With Hematopoietic Stem Cell Transplantation Due to Chronic Granulomatous Disease.

J Pediatr Hematol Oncol 2019 Apr;41(3):e161-e163

Department of Pediatric Bone Marrow Transplantation, Ege University Faculty of Medicine, İzmir, Turkey.

Allergic bronchopulmonary aspergillosis is an immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. This disorder is most commonly seen in patients with poorly controlled asthma and cystic fibrosis. It is rarely reported in chronic granulomatous disease patients; however, there are no cases reported with hematopoietic stem cell transplantation in the English literature. Herein, we report a patient with chronic granulomatous disease who had hematopoietic stem cell transplantation and subsequently developed allergic bronchopulmonary aspergillosis.
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http://dx.doi.org/10.1097/MPH.0000000000001252DOI Listing
April 2019

Is there an increased risk of spinal relapse in standard-risk medulloblastoma/primitive neuroectodermal tumor patients who receive only a reduced dose of craniospinal radiotherapy?

Childs Nerv Syst 2018 09 4;34(9):1657-1662. Epub 2018 Jun 4.

Faculty of Medicine, Department of Radiation Oncology, Ege University, İzmir, Turkey.

Purpose: Medulloblastoma (MBL) is the most common pediatric brain malignancy. Postoperative radiotherapy to the entire craniospinal axis is the standard-of-care but has linked to long-term morbidity. In this study, we analyzed the implication of reduced dose craniospinal radiotherapy (RT) for survival and pattern of relapse in MBL patients.

Material And Methods: The clinical characteristics of 32 consecutively diagnosed medulloblastoma/primitive neuroectodermal tumor patients were analyzed. After surgical resection, a dose of 23.4 Gy of spinal RT with a posterior fossa boost of 30.6 Gy was prescribed to standard-risk patients, whereas high-risk patients received 36 Gy spinal RT with additional boosts to the posterior fossa up to 54 Gy. Then, both groups received the same chemotherapy protocol.

Results: Five-year OS for standard and high-risk patients was 94 and 50%, respectively. When analyzing prognostic factors, postoperative tumor size is the most important one which affects the OS. Ten patients relapsed during follow-up, and there was no isolated spinal relapse in either group.

Conclusion: The risk of isolated spinal relapse does not increase with reduced-dose craniospinal RT, since there is no isolated relapse in either the standard or high-risk groups of patients.
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http://dx.doi.org/10.1007/s00381-018-3842-6DOI Listing
September 2018

Risks and outcomes of invasive fungal infections in pediatric allogeneic hematopoietic stem cell transplant recipients receiving fluconazole prophylaxis: a multicenter cohort study by the Turkish Pediatric Bone Marrow Transplantation Study Group.

Med Mycol 2019 Feb;57(2):161-170

Department of Pediatric Hematology&Oncology and BMT Unit, Medical Park Antalya Hospital, Antalya.

Invasive fungal infections (IFIs) are a major cause of infection-related morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data from pediatric settings are scarce. To determine the incidence, risk factors and outcomes of IFIs in a 180-day period post-transplantation, 408 pediatric patients who underwent allogeneic HSCT were retrospectively analyzed. The study included only proven and probable IFIs. The cumulative incidences of IFI were 2.7%, 5.0%, and 6.5% at 30, 100, and 180 days post-transplantation, respectively. According to the multivariate analysis, the factors associated with increased IFI risk in the 180-day period post-HSCT were previous HSCT history (hazard ratio [HR], 4.57; 95% confidence interval [CI] 1.42-14.71; P = .011), use of anti-thymocyte globulin (ATG) (HR, 2.94; 95% CI 1.27-6.80; P = .012), grade III-IV acute graft-versus-host-disease (GVHD) (HR, 2.91; 95% CI 1.24-6.80; P = .014) and late or no lymphocyte engraftment (HR, 2.71; 95% CI 1.30-5.62; P = .007). CMV reactivation was marginally associated with an increased risk of IFI development (HR, 1.91; 95% CI 0.97-3.74; P = .063). IFI-related mortality was 1.5%, and case fatality rate was 27.0%.The close monitoring of IFIs in pediatric patients with severe acute GVHD who receive ATG during conditioning is critical to reduce morbidity and mortality after allogeneic HSCT, particularly among those with prior HSCT and no or late lymphocyte engraftment.
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http://dx.doi.org/10.1093/mmy/myy015DOI Listing
February 2019

Post-transplant malignancies in pediatric liver transplant recipients: Experience of two centers in Turkey.

Turk J Gastroenterol 2018 01;29(1):89-93

Department of Pediatric Gastroenterology, Hepatology and Nutrition, Ege University School of Medicine, İzmir, Turkey.

Background/aims: A liver transplant is the preferred treatment for patients with end-stage liver disease, as it usually results in longterm survival. However, due to the use of chronic immunosuppressive therapy, which is necessary to prevent rejection, de novo cancer is a major risk after transplantation. The aim of this study was to assess the incidence of post-transplant malignancies in children after liver transplantations.

Materials And Methods: The study group consisted of 206 liver transplant recipients, with no history of cancer, including hepatocellular carcinoma, in two liver transplantation centers in Turkey between 1997 and 2015. Data were obtained from patient's data chart.

Results: In the study group, de novo cancer was diagnosed in 13 of the 206 patients. Post-transplant lymphoproliferative disease (PTLD) occurred in seven (53.8%) patients and other malignancies in six of the 13 patients. The types of PTLD were as follows: B-cell origin (n=2), Epstein-Barr virus (EBV)-related (n=2), T-cell origin (n=1), and Hodgkin's lymphoma (n=2). EBV DNA was isolated from seven patients, three of whom developed PTLD. The others developed Kaposi's sarcomas, Burkitt's lymphomas, cutaneous large-cell lymphomas, Hodgkin's lymphomas, and liver sarcomas.

Conclusion: After transplantation, immunosuppressive treatment is unavoidable, increasing the risk of malignancies. However, a close follow-up and periodic screening can reduce cancer-related mortality and morbidity.
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http://dx.doi.org/10.5152/tjg.2017.17089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322611PMC
January 2018

Treatment of high-risk neuroblastoma: National protocol results of the Turkish Pediatric Oncology Group.

J Cancer Res Ther 2017 Apr-Jun;13(2):284-290

Department of Pediatric Oncology, Dokuz Eylul University Institute of Oncology, Izmir, Turkey.

Background: The national protocol aimed to improve the outcome of the high risk neuroblastoma patients by high-dose chemotherapy and stem cell rescue with intensive multimodal therapy.

Materials And Methods: After the 6 induction chemotherapy cycles, patients without disease progression were nonrandomly (by physicians' and/or parent's choices) allocated into two treatment arms, which were designed to continue the conventional chemotherapy (CCT), or myeloablative therapy with autologous stem cell rescue (ASCR).

Results: Fifty-six percent (272 patients) of patients was evaluated as high risk. Response rate to induction chemotherapy was 71%. Overall event-free survival (EFS) and overall survival (OS) at 5 years were 28% and 36%, respectively. "As treated" analysis documented postinduction EFS of 41% in CCT arm (n = 138) and 29% in ASCR group (n = 47) (P = 0.042); whereas, OS was 45% and 39%, respectively (P = 0.05). Thirty-one patients (11%) died of treatment-related complications.

Conclusion: Survival rates of high-risk neuroblastoma have improved in Turkey. Myeloablative chemotherapy with ASCR has not augmented the therapeutic end point in our country's circumstances. The adequate supportive care and the higher patients' compliance are attained, the better survival rates might be obtained in high-risk neuroblastoma patients received myeloablative chemotherapy and ASCR.
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http://dx.doi.org/10.4103/0973-1482.183205DOI Listing
April 2018

Risk factors predicting the survival of pediatric patients with relapsed/refractory non-Hodgkin lymphoma who underwent hematopoietic stem cell transplantation: a retrospective study from the Turkish pediatric bone marrow transplantation registry.

Leuk Lymphoma 2018 01 2;59(1):85-96. Epub 2017 Jun 2.

c Faculty of Medicine, Göztepe Medical Park Hospital , Bahçeşehir University , Istanbul, Turkey.

We examined outcomes of 62 pediatric patients with relapsed or refractory non-Hodgkin lymphoma (rr-NHL) who underwent hematopoietic stem cell transplantation (HSCT). The overall survival (OS) and event-free survival (EFS) rates were 65% and 48%, respectively. Survival rates for patients with chemosensitive disease at the time of HSCT were significantly higher than those of patients with chemoresistant disease (69% vs. 37%, p = .019 for OS; 54% vs. 12%, p < .001 for EFS; respectively). A chemoresistant disease at transplantation was the only factor that predicted a limited OS (hazard ratio = 10.00) and EFS (hazard ratio = 16.39) rates. Intensive chemotherapy followed by HSCT could be an effective strategy for treating children with rr-NHL and may offer improved survival for a significant group of pediatric patients, particularly those with chemosensitive disease at transplantation.
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http://dx.doi.org/10.1080/10428194.2017.1330472DOI Listing
January 2018

Hematopoietic Stem Cell Transplantation Using Preimplantation Genetic Diagnosis and Human Leukocyte Antigen Typing for Human Leukocyte Antigen-Matched Sibling Donor: A Turkish Multicenter Study.

Biol Blood Marrow Transplant 2017 May 10;23(5):790-794. Epub 2017 Feb 10.

Turkish Pediatric Bone Marrow Transplantation Study Group. Bahçeşehir University Medical Faculty, Medical Park Göztepe Hospital, Istanbul, Turkey.

Preimplantation genetic diagnosis involves the diagnosis of a genetic disorder in embryos obtained through in vitro fertilization, selection of healthy embryos, and transfer of the embryos to the mother's uterus. Preimplantation genetic diagnosis has been used not only to avoid the risk of having an affected child, but it also offers, using HLA matching, preselection of potential HLA-genoidentical healthy donor progeny for an affected sibling who requires bone marrow transplantation. Here, we share the hematopoietic stem cell transplantation results of 52 patients with different benign and malign hematological or metabolic diseases or immunodeficiencies whose donors were siblings born with this technique in Turkey since 2008. The median age of the patients' at the time of the transplantation was 8 years (range, 3 to 16 years) and the median age of the donors was 2 years (range, .5 to 6 years). The most common indication for HSCT was thalassemia major (42 of all patients, 80%). The stem cell source in all of the transplantations was bone marrow. In 37 of the transplantations, umbilical cord blood of the same donor was also used. In 50 of the 52 patients, full engraftment was achieved with a mean of 4.6 × 10 CD 34 cells per kg of recipient weight. Ninety-six percent of the patients have been cured through hematopoietic stem cell transplantation without any complication. Primary engraftment failure was seen in only 2 patients with thalassemia major. All of the donors and the patients are alive with good health status. Preimplantation genetic diagnosis with HLA matching offers a life-saving chance for patients who need transplantation but lack an HLA genoidentical donor.
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http://dx.doi.org/10.1016/j.bbmt.2017.02.002DOI Listing
May 2017

Early Diagnosis and Hematopoietic Stem Cell Transplantation for IL10R Deficiency Leading to Very Early-Onset Inflammatory Bowel Disease Are Essential in Familial Cases.

Case Reports Immunol 2016 6;2016:5459029. Epub 2016 Sep 6.

Faculty of Medicine, Department of Pediatric Immunology, Ege University, Izmir, Turkey.

Alterations of immune homeostasis in the gut may result in development of inflammatory bowel disease. A five-month-old girl was referred for recurrent respiratory and genitourinary tract infections, sepsis in neonatal period, chronic diarrhea, perianal abscess, rectovaginal fistula, and hyperemic skin lesions. She was born to second-degree consanguineous, healthy parents. Her elder siblings were lost at 4 months of age due to sepsis and 1 year of age due to inflammatory bowel disease, respectively. Absolute neutrophil and lymphocyte counts, immunoglobulin levels, and lymphocyte subsets were normal ruling out severe congenital neutropenia and classic severe combined immunodeficiencies. Quantitative determination of oxidative burst was normal, excluding chronic granulomatous disease. Colonoscopy revealed granulation, ulceration, and pseudopolyps, compatible with colitis. Very early-onset colitis and perianal disease leading to fistula formation suggested probability of inherited deficiencies of IL-10 or IL-10 receptor. A mutation at position c.G477A in exon of the gene, resulting in a stop codon at position p.W159X, was identified. The patient underwent myeloablative hematopoietic stem cell transplantation from full matched father at 11 months of age. Perianal lesions, chronic diarrhea, and recurrent infections resolved after transplantation. IL-10/IL-10R deficiencies must be considered in patients with early-onset enterocolitis.
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http://dx.doi.org/10.1155/2016/5459029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028855PMC
September 2016

Prognostic Factors and a New Prognostic Index Model for Children and Adolescents with Hodgkin's Lymphoma Who Underwent Autologous Hematopoietic Stem Cell Transplantation: A Multicenter Study of the Turkish Pediatric Bone Marrow Transplantation Study Group.

Turk J Haematol 2016 Dec 18;33(4):265-272. Epub 2016 Apr 18.

Gülhane Training and Research Hospital Clinic of Pediatric Oncology, Ankara, Turkey Phone: +90 312 304 43 94 E-mail:

Objective: The prognostic factors and a new childhood prognostic index after autologous hematopoietic stem cell transplantation (AHSCT) in patients with relapsed/refractory Hodgkin's lymphoma (HL) were evaluated.

Materials And Methods: The prognostic factors of 61 patients who underwent AHSCT between January 1990 and December 2014 were evaluated. In addition, the Age-Adjusted International Prognostic Index and the Childhood International Prognostic Index (CIPI) were evaluated for their impact on prognosis.

Results: The median age of the 61 patients was 14.8 years (minimum-maximum: 5-20 years) at the time of AHSCT. There were single relapses in 28 patients, ≥2 relapses in eight patients, and refractory disease in 25 patients. The chemosensitivity/chemorefractory ratio was 36/25. No pretransplant radiotherapy, no remission at the time of transplantation, posttransplant white blood cell count over 10x103/µL, posttransplant positron emission tomography positivity at day 100, and serum albumin of <2.5 g/dL at diagnosis were correlated with progression-free survival. No remission at the time of transplantation, bone marrow positivity at diagnosis, and relapse after AHSCT were significant parameters for overall survival.

Conclusion: The major factors affecting the progression-free and overall survival were clearly demonstrated. A CIPI that uses a lactate dehydrogenase level of 500 IU/L worked well for estimating the prognosis. We recommend AHSCT at first complete remission for relapsed cases, and it should also be taken into consideration for patients with high prognostic scores at diagnosis.
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http://dx.doi.org/10.4274/tjh.2015.0280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204179PMC
December 2016

Outcome of autologous hematopoietic stem cell transplantation in children and adolescents with relapsed or refractory Hodgkin's lymphoma.

Pediatr Transplant 2015 Nov 8;19(7):745-52. Epub 2015 Sep 8.

Pediatric BMT Units, Bahcesehir University Faculty of Medicine Medical Park Goztepe Hospital, Istanbul, Turkey.

This study evaluates the outcome of 66 pediatric patients with rrHL who underwent autoHSCT. Twenty-nine patients experienced early relapse, and 19 patients experienced late relapse. Of 18 newly diagnosed with HL, 13 were primary refractory disease and five had late responsive disease. At the time of transplantation, only 68% of the patients were chemosensitive. The majority of patients received BCNU + etoposide + ara-C + melphalan for conditioning (45/66), and peripheral blood (56/66) was used as a source of stem cells. After a median follow-up period of 39 months, 46 patients were alive. At five yr, the probabilities of OS, EFS, the relapse rate, and the non-relapse mortality rate were 63.1%, 54.3%, 36.4%, and 9.1%, respectively. The probability of EFS in chemosensitive and chemoresistant patients at five yr was 72.3% and 19%, respectively (p < 0.001). Multivariate analysis showed that chemoresistant disease at the time of transplantation was the only factor predicting limited both OS (hazard ratio = 4.073) and EFS (hazard ratio = 4.599). AutoHSCT plays an important role for the treatment of rrHL in children and adolescents, and survival rates are better for patients with chemosensitive disease at the time of transplantation.
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http://dx.doi.org/10.1111/petr.12573DOI Listing
November 2015

Cutaneous side effects of chemotherapy in pediatric oncology patients.

Cutis 2015 Jan;95(1):11-6

Ege University, Department of Dermatology and Venereology, 35040 Bornova, Izmir, Turkey.

Pediatric oncology patients can present with various skin lesions related to both primary disease and immunosuppressive treatments. This study aimed to evaluate the cutaneous side effects of chemotherapy in pediatric oncology patients. Sixty-five pediatric oncology patients who were scheduled to undergo chemotherapy from May 2011 to May 2013 were included in the study. Three patients were excluded from the results, as 2 patients died during treatment and 1 patient withdrew from the study; therefore, a total of 62 patients were evaluated for mucocutaneous findings. Patients were grouped according to their oncological diagnoses and a statistical analysis was performed. There was no statistical significance in the incidence of cutaneous side effects of chemotherapy among the different diagnostic groups. Awareness among dermatologists of the possible cutaneous side effects of chemotherapy in pediatric patients and their causes can promote early diagnosis and treatment in this patient population.
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January 2015

Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency.

J Allergy Clin Immunol 2015 Apr 14;135(4):988-997.e6. Epub 2015 Jan 14.

Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg and the University of Freiburg, Freiburg, Germany. Electronic address:

Background: Common variable immunodeficiency (CVID) is usually well controlled with immunoglobulin substitution and immunomodulatory drugs. A subgroup of patients has a complicated disease course with high mortality. For these patients, investigation of more invasive, potentially curative treatments, such as allogeneic hematopoietic stem cell transplantation (HSCT), is warranted.

Objective: We sought to define the outcomes of HSCT for patients with CVID.

Methods: Retrospective data were collected from 14 centers worldwide on patients with CVID receiving HSCT between 1993 and 2012.

Results: Twenty-five patients with CVID, which was defined according to international criteria, aged 8 to 50 years at the time of transplantation were included in the study. The indication for HSCT was immunologic dysregulation in the majority of patients. The overall survival rate was 48%, and the survival rate for patients undergoing transplantation for lymphoma was 83%. The major causes of death were treatment-refractory graft-versus-host disease accompanied by poor immune reconstitution and infectious complications. Immunoglobulin substitution was stopped in 50% of surviving patients. In 92% of surviving patients, the condition constituting the indication for HSCT resolved.

Conclusion: This multicenter study demonstrated that HSCT in patients with CVID was beneficial in most surviving patients; however, there was a high mortality associated with the procedure. Therefore this therapeutic approach should only be considered in carefully selected patients in whom there has been extensive characterization of the immunologic and/or genetic defect underlying the CVID diagnosis. Criteria for patient selection, refinement of the transplantation protocol, and timing are needed for an improved outcome.
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http://dx.doi.org/10.1016/j.jaci.2014.11.029DOI Listing
April 2015

Combined cord blood and bone marrow transplantation from the same human leucocyte antigen-identical sibling donor for children with malignant and non-malignant diseases.

Br J Haematol 2015 Apr 18;169(1):103-10. Epub 2014 Dec 18.

Hospital Saint Louis, AP-HP, and IUH University Paris VII, Eurocord, Paris, France; Centro de Oncologia, Hospital Sirio-Libanes, Sao Paulo, Brazil.

Umbilical cord blood (UCB) from an human leucocyte antigen (HLA)-identical sibling can be used for transplantation of patients with malignant and non-malignant diseases. However, the low cellular content of most UCB units represents a limitation to this approach. An option to increase cell dose is to harvest bone marrow (BM) cells from the same donor and infuse them along with the UCB. We studied 156 children who received such a combined graft between 1992 and 2011. Median age was 7 years and 78% of patients (n = 122) were transplanted for non-malignant diseases, mainly haemoglobinopathies. Acute leukaemia (n = 26) was the most frequent malignant diagnosis. Most patients (91%) received myeloablative conditioning. Median donor age was 1·7 years, median infused nucleated cell dose was 24·4 × 10(7) /kg and median follow-up was 41 months. Sixty-days neutrophil recovery occurred in 96% of patients at a median of 17 d. The probabilities of grade-II-IV acute and chronic graft-versus-host disease (GVHD) were 19% and 10%, respectively. Four-year overall survival was 90% (68% malignant; 97% non-malignant diseases) with 3% probability of death. In conclusion, combined UCB and BM transplantation from an HLA-identical sibling donor is an effective treatment for children with malignant and non-malignant disorders with high overall survival and low incidence of GVHD.
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http://dx.doi.org/10.1111/bjh.13267DOI Listing
April 2015

Successful haematopoietic stem cell transplantation in 44 children from healthy siblings conceived after preimplantation HLA matching.

Reprod Biomed Online 2014 Sep 12;29(3):340-51. Epub 2014 Jun 12.

ART and Reproductive Genetics Center, Istanbul Memorial Hospital, Istanbul, Turkey.

Haematopoietic stem cell transplantation (HSCT) remains the best therapeutic option for many acquired and inherited paediatric haematological disorders. Unfortunately, the probability of finding an HLA matched donor is limited. An alternative technique is PGD combined with HLA matching, which offers the possibility of selecting unaffected embryos that are HLA compatible with the sick child, with the aim of possible use of stem cells from the resulting baby in future. Since the first successful report for Fanconi anaemia a decade ago, the therapeutic success of this technique was reported in a few cases and for a limited number of disorders. Here, we report full recovery of 44 sick children who received HSCT from healthy infants conceived after pre-implantation HLA matching for the following 10 indications; beta-thalassaemia, Wiskott-Aldrich syndrome, Fanconi anaemia, sickle cell anaemia, acute myeloid leukaemia, acute lymphoblastic leukaemia, Glanzmann's thrombasthaenia, Diamond-Blackfan anaemia, X-linked adrenoleukodystrophy and mucopolysaccharidosis type I. No serious complications were observed among recipients and donors. Graft failure occurred in four children with beta-thalassaemia where a second HSCT was planned. Preimplantation HLA matching is a reliable technique and provides a realistic option for couples seeking treatment for an affected child when no HLA-matched donor is available.
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http://dx.doi.org/10.1016/j.rbmo.2014.05.010DOI Listing
September 2014

Prospective evaluation of whole genome microRNA expression profiling in childhood acute lymphoblastic leukemia.

Biomed Res Int 2014 14;2014:967585. Epub 2014 May 14.

Department of Pediatrics, Faculty of Medicine, Ege University, 35100 Izmir, Turkey.

Dysregulation of microRNA (miRNA) expression contributes to the pathogenesis of several clinical conditions. The aim of this study is to evaluate the associations between miRNAs and childhood acute lymphoblastic leukemia (ALL) to discover their role in the course of the disease. Forty-three children with ALL and 14 age-matched healthy controls were included in the study. MicroRNA microarray expression profiling was used for peripheral blood and bone marrow samples. Aberrant miRNA expressions associated with the diagnosis and outcome were prospectively evaluated. Confirmation analysis was performed by real time RT-PCR. miR-128, miR-146a, miR-155, miR-181a, and miR-195 were significantly dysregulated in ALL patients at day 0. Following a six-month treatment period, the change in miRNA levels was determined by real time RT-PCR and expression of miR-146a, miR-155, miR-181a, and miR-195 significantly decreased. To conclude, these miRNAs not only may be used as biomarkers in diagnosis of ALL and monitoring the disease but also provide new insights into the potential roles of them in leukemogenesis.
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http://dx.doi.org/10.1155/2014/967585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053274PMC
February 2015

Determination of school-related problems in children treated for cancer.

J Sch Nurs 2014 Oct 27;30(5):376-84. Epub 2013 Sep 27.

Pediatric Oncology Department, Ege University Faculty of Medicine, Izmir, Turkey.

This descriptive and case-control study was carried out in a pediatric oncology outpatient clinic to determine the school-related physical, social, and psychological problems and problems experienced in academic achievement of children treated for cancer. The sample of the study consisted of 56 Turkish patients with cancer, aged 7-18 years, who were in remission and attending school as well as their parents, a control group of patients who did not have cancer, and their teachers. A Child Information Form, a Child Health Questionnaire Parent's Form of 50 questions, a Behavior Evaluation Scale for Children, and Young People and a Teacher's Report Form were used as data collection tools in the study. Of the children, 30.3% experienced various physical difficulties stemming from cancer therapy that affected their school life. The number of late enrollments, the number of children repeating a grade, and the rates of school absenteeism were also found to be higher in the survivors than in the controls.
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http://dx.doi.org/10.1177/1059840513506942DOI Listing
October 2014

Enteral nutrition is feasible in pediatric stem cell transplantation patients.

Pediatr Blood Cancer 2012 Dec 21;59(7):1327-9. Epub 2012 Aug 21.

Division of Nutrition, Pediatric Bone Marrow Transplantation Unit, Ege University School of Medicine, IZMIR, Turkey.

We aimed to demonstrate whether enteral nutrition (EN) is feasible in daily practice of hematopoietic stem cell transplantation (HSCT).Nutritional records of 100 patients were evaluated. Patients with poor oral intake were fed by EN with tube. A total of 79 patients required nutritional support. Of them, 71 were fed by EN only. Five were fed by EN plus parenteral nutrition (PN),three were fed by PN only. Median duration of EN was 21 days. In the EN only group, 68% gained or maintained their weight. EN should be considered as a feasible option for nutrition support in children undergoing HSCT.
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http://dx.doi.org/10.1002/pbc.24275DOI Listing
December 2012

Complications of central venous catheters in children undergoing hematopoietic stem cell transplantation in Turkey.

J Pediatr Oncol Nurs 2012 Jul-Aug;29(4):199-205

Izmir Katip Celebi University, Izmir, Turkey.

Although central venous catheters (CVCs) have become an integral element of the care of patients undergoing hematopoietic stem cell transplantation (HSCT), the associated complications can lead to treatment delays and negatively affect the child and family's quality of life. The aim of this study was to identify the types, rate of, and risk factors for the complications relating to CVCs used in children undergoing HSCT in Turkey. One hundred children were followed prospectively to track catheter-related complications in the transplantation unit. Overall, 186 complications were documented. The most frequent complications were catheter-related infections and malfunctions. Children who had nonhematological disease had a higher rate of complications than those with hematological disease. HSCT nurses should follow and apply evidence-based clinical practice guidelines to support the management of catheters. Nurse staffing ratios and workload may be an issue in developing countries. The authors believe that proper maintenance of CVCs contributes to the reduction of catheter-related complications despite these issues and that problems can be overcome by hiring experienced staff, appropriate nursing education, and by organizing and improving home care programs for HSCT patients.
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http://dx.doi.org/10.1177/1043454212451366DOI Listing
November 2012

Late-onset graft-versus-host disease after pediatric living-related liver transplantation for Langerhans cell histiocytosis.

Pediatr Transplant 2011 Sep 24;15(6):E105-9. Epub 2009 Feb 24.

Department of Pediatric Gastroenterology, Ege University School of Medicine, Izmir, Turkey.

GVHD is the most common and well-known cause of morbidity and mortality following allogeneic BM transplantation. The GVHD following OLT is an uncommon complication but has a high mortality and poses a major diagnostic and therapeutic challenge. We herein discussed a 12-month-old girl with multi-system LCH, who developed end-stage liver disease despite intensive chemotherapy. She underwent ABO-compatible liver transplantation at 28 months while in remission from LCH. The donor was her 26-yr-old father. Post-operative course was uneventful. The GVHD manifested with skin rash and BM suppression on post-transplant day 94 and confirmed by both microchimerism and skin biopsy. Prednisolone, basiliximab, and ATG were administered immediately but the bone marrow suppression was not improved and the patient died because of Candida sepsis at six-month post-transplant. GVHD after OLT should be keep in mind in patients with rash and BM suppression after liver transplantation. In LDLT, a patient who carries risk factors should investigated for optimal HLA matching.
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http://dx.doi.org/10.1111/j.1399-3046.2008.00899.xDOI Listing
September 2011

The Association of minor congenital anomalies and childhood cancer.

Pediatr Blood Cancer 2011 Jul 25;56(7):1098-102. Epub 2011 Feb 25.

Department of Medical Genetics, Ege University Faculty of Medicine, Izmir, Turkey.

Background: Although the association of some congenital malformations and specific genetic syndromes is well understood, the association between minor anomalies and cancer is not well known. In recent years some researchers have reported studies establishing this association in different types of cancer. In this study, we aimed to investigate the prevalence and patterns of age-independent minor anomalies in childhood cancer patients.

Procedure: Two hundred patients with various types of cancer and 200 healthy controls were examined by two different medical geneticists for minor anomalies who evaluated all the cases and controls simultaneously. Besides minor anomalies, information on the consanguinity between the parents and occurrence of cancer in relatives were also recorded. The types of minor anomalies in different types of cancer, the number of minor anomalies in patients and controls, the association between cancer and the occurrence of different types of minor anomalies were also evaluated.

Results: The consanguinity and the history of cancer in relatives were significantly more prevalent in patients (P = 0.04 and P < 0.001, respectively). The number of minor anomalies in patients were significantly higher compared to the controls (P < 0.01). Particularly, the presence of hypertelorism, high-arched palate (approximately 40-fold higher, 95% CI: 12.895-125.037) and hand-foot anomalies were found to be more prevalent in patients having cancer compared to the controls.

Conclusion: The common pathways during the embryogenesis may play a role in the development of cancer. The presence and the combination of minor anomalies seem to be associated with a higher prevalence of cancer.
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http://dx.doi.org/10.1002/pbc.23049DOI Listing
July 2011

Sustained seroconversion of chronic hepatitis B infection after stem cell transplantation.

Pediatr Transplant 2011 Aug 20;15(5):E92-5. Epub 2010 Jan 20.

Ege University, Pediatric Oncology and Bone Marrow Transplantation Unit Ege University, Pediatric Gastroenterology, Hepatology and Nutrition, Izmir, Turkey.

  We present an 18-yr-old adolescent with acute lymphocytic leukemia, who underwent peripheral blood SCT with serologically and histologically documented chronic hepatitis B infection. Prior and during the transplant process, lamivudine was administered orally and he underwent SCT with a twofold decrease in viral load at the time of transplant from his HLA full matched, HBV natural immune (anti-HBs and anti-HBc positive) donor. Successful engraftment was achieved and three months after SCT, HBV seroconversion was documented accompanied with an ALT flare. Chronic graft-versus-host disease coincided after the transplantation, and he has been on immunosuppressive treatment for 25 months with sustained HBV seroconversion. We assume that adoptive immunity transfer combined with antiviral treatment might also constitute sustained seroconversion in chronic HBV, besides the reported risk of reactivation.
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http://dx.doi.org/10.1111/j.1399-3046.2009.01272.xDOI Listing
August 2011

Diverse phenotypic and genotypic presentation of RAG1 mutations in two cases with SCID.

Clin Exp Med 2009 Dec 21;9(4):339-42. Epub 2009 May 21.

Department of Pediatrics, Faculty of Medicine, Ege University, 35100, Bornova, Izmir, Turkey.

Severe combined immunodeficiencies (SCID) comprise a spectrum of genetic defects that involve both humoral and cellular immunities. Defects in recombinating activating gene 1 (RAG1), RAG2, Artemis, or LIG4 can disrupt V(D)J recombination. Defective V(D)J recombination of the T and B cell receptors is responsible for T(-)B(-)NK(+)SCID. Amorphic mutations in RAG1 and RAG2 cause T(-)B(-)NK(+)SCID, whereas hypomorphic mutations cause an immunodeficency characterized by oligoclonal expansion of TCRgammadelta T cells, severe CMV infection and autoimmunity. First patient is a typical T(-)B(-)NK(+)SCID with clinical and immunologic findings while the second is atypical with normal immunoglobulin levels, CD4 lymphopenia, elevated TCRgammadelta T cells, persistent CMV infection, and autoimmune hemolytic anemia. These cases are presented to emphasize that mutations in RAG1 gene may lead to a diverse spectrum of clinical and immunologic findings while hypomorphic mutations may be related with autoimmunity and refractory CMV infection during infancy.
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http://dx.doi.org/10.1007/s10238-009-0053-1DOI Listing
December 2009

Methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms and therapy-related toxicity in children treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma.

Leuk Lymphoma 2009 Jun;50(6):912-7

Pediatric Oncology Department and Pediatric BMT Center, Ege University School of Medicine, Bornova, Izmir, Turkey.

This study aimed to investigate the association of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms with serum drug levels and toxicities after high-dose methotrexate (MTX) infusion. The study included 37 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma. Serum MTX levels and toxicities of bone marrow, liver and kidney were analysed. Genotype analysis of the C677T and A1298C gene polymorphisms from genomic DNA of the subjects was performed by real-time PCR. Subjects with MTHFR polymorphism for C677T (CT, TT) had significantly higher MTX levels at 24 h (p = 0.009), and these genotypes did not seem to cause toxicity. Subjects with MTHFR polymorphism for A1298C (AC, CC) had significantly higher MTX levels at 48 h (p = 0.02), and had more grade III/IV anemia (p = 0.02), thrombocytopenia (p = 0.0001), elevated AST levels (p = 0.04) and frequent febrile neutropenic episodes (p = 0.004). The present study suggests that A1298C gene, but not C677T polymorphism is associated with MTX-related toxicity.
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http://dx.doi.org/10.1080/10428190902893819DOI Listing
June 2009