Nivolumab is an inhibitor of programmed cell death 1 (PD-1), which enables activated T cells to attack the tumor cells. Although the utilization of nivolumab in adulthood cancers is more common, experience in childhood has been increasing recently. Herein, pediatric cases received nivolumab for distinct cancers are presented. The data of nine patients under the age of 18 years who received nivolumab for various cancers in the Pediatric Oncology clinic between January 2019-December 2022 were obtained. Nivolumab was administered intravenously at a dose of 3 mg/kg with 30 minutes infusion every two weeks. Patients' clinical, cancer types, response to primary treatment, comorbidities, and outcomes of nivolumab were evaluated. Nivolumab was utilized for non-Hodgkin lymphoma, classical Hodgkin lymphoma (cHL), central nervous system, germ cell and gastrointestinal system cancers. Four out of nine patients had constitutional mismatch repair deficiency (CMMRD) syndrome and 2/4 patients developed secondary cancers during the nivolumab. The median dose and duration of nivolumab were 10 doses (4-32 doses) and 6 months (2 to 17 months), respectively. The median follow-up period was 25 months (2-46 months). Nivolumab achieved progression free survival in immature teratoma, cHL and T-Lymphoblastic lymphoma (T-LBL) with 46 months, 22 months, and 31 months, respectively. Only one patient had severe generalize edema attributed to nivolumab. We observed that although encouraging outcomes with nivolumab in cHL, immature teratoma and T-LBL, it failed to prevent glioblastoma progression in children with CMMRD. In summary, nivolumab may be effective in selected childhood cancers.

Case report: The 22-month-old male and 15-day-old female patients presented with persistent stridor since birth. Tracheoscopy of the first patient revealed a 90% obstructing hemangioma in the subglottic area, while the second patient's CT scan showed a hemangioma at the subglottic level. Both patients were initiated on propranolol therapy. These cases highlight the significance of subglottic hemangioma as a treatable cause of stridor in infants and emphasize the importance of propranolol treatment.

Aim: Hemophilias are inherited bleeding disorders, in which the patients generally present with clinical complaints of hemarthrosis. Intracranial hemorrhage (ICH) is one of the severe bleeding types with the highest mortality and morbidity throughout childhood, as well as in patients with a diagnosis of hemophilia. Herein, a single-center experience of intracranial hemorrhage in children with hemophilia is presented. Materials and Methods: The files and hospital records of the patients with the diagnosis of hemophilia who were followed up by the Pediatric Hematology and Oncology Department of Erciyes University between the years 1993-2022 were evaluated retrospectively. Results: A total of 81 patients with hemophilia were evaluated. Among them, 9 patients developed ICH. All patients had severe diseases. The mean age of incidence ICH was 2,6 months (4 days- 8,7 months). All the ICH episodes were observed within the first year of life. Four patients were diagnosed with the ICH episode initially. None of the patients had primary prophylaxis. The majority of them were admitted with neurological signs and symptoms. There was no ICH-related mortality in our study and all of the patients are being followed up in our department. Conclusion: Intracranial hemorrhage remains important in patients with congenital bleeding disorders, especially in hemophilia; with difficulties in diagnosis, management, and treatment.

Triosephosphate isomerase deficiency is an autosomal recessive disorder characterized by progressive neuromuscular degeneration, seizure, dystonia, weak muscles, cardiomyopathy, hemolytic anemia, and death in early childhood. In the glycolytic pathway, dihydroxy acetone phosphate (DHAP) is converted to glyceraldehyde-3-phosphate by an enzymatic reaction. The reaction is catalyzed by the TPI enzyme. In TPI deficiency, erythrocyte viability is reduced due to insufficient anaerobic respiration and DHAP accumulation causes toxic effects on cells. A 2-month-old boy initially presented with infection and moderate anemia. Respiratory distress and neurological symptoms developed shortly thereafter. He was followed up with a mechanical ventilator for a long time. A homozygous pathogenic variant in the TPI1 gene was detected in the genetic analysis performed due to the progressive neurodegeneration and the need of intermittent erythrocyte transfusion in the follow-up. Here, an infant case with triosephosphate isomerase enzyme deficiency is presented.

Objective: Mutations in IKZF1, which encodes Ikaros family zinc finger 1 (IKAROS) transcription factor, are associated with recurrent infections, cytopenia, autoimmune diseases, and hematologic malignancies. Diverse clinical phenotypes resulting from IKZF1 mutations include pulmonary fungal infections, cytopenia, autoimmune hemolytic anemia (AIHA), and malignancies. In this study, we aimed to assess the DNA-binding ability and pericentromeric (PC) localization of a variant of IKZF discovered in a patient. Materials and Methods: DNA-binding ability of a pathogenic IKZF variant was tested using electrophoretic mobility shift assay and PC localization of the variant was assessed by immunofluorescent microscopy in NIH3T3 cells. Results: Clinical features of a 3-month-old male infant who underwent hematopoietic stem cell transplantation because of an IKZF1 mutation-associated common variable immunodeficiency, AIHA, and pancytopenia are described. DNA studies revealed a heterozygous missense variant (IKZF1 NM_006060 c.427C>T; p.R143W). Cotransfection studies revealed that mutant R143W has a partial dominant-negative effect over PC targeting and DNA binding. Conclusions: IKZF1 mutation must be kept in mind if neonatal AIHA, common variable immunodeficiency, and pancytopenia are observed.

Background: Type 2B von Willebrand disease (VWD) is a hereditary bleeding disorder caused by changes in the von Willebrand factor (VWF), which increases the binding of VWF to platelets. Type 2B VWD may present with thrombocytopenia. Case Report: A four-day-old newborn was brought to the neonatal intensive care unit presenting with bleeding and severe thrombocytopenia. The platelet level was 10,000/mm(3), and coagulation tests were normal. There were no clinical evidence of sepsis; therefore, alloimmune or autoimmune thrombocytopenia was suspected. When we found out that her mother and relatives had intermittent thrombocytopenia, advanced tests were performed. Ristocetin cofactor activity was low; type 2 VWD was considered. Using low-dose ristocetin, we increased platelet aggregation. Heterozygous c.3946G > A (p.Val-1316Met) mutation was detected, and type 2B VWD was diagnosed. Conclusion: Type 2B VWD may cause a diagnostic problem in the differential diagnosis of neonatal thrombocytopenia including neonatal autoimmune thrombocytopenia.

Objective: The programmed cell death 1 (PD-1) receptor is an immune checkpoint receptor expressed by activated T cells. PD-1 inhibits the immune system by binding to its ligands expressed on tumor cells. Nivolumab and pembrolizumab are some of the monoclonal antibodies that inhibit the PD-1. We present our experience with eight cases which were treated with nivolumab for different malignant diseases in our clinic. Methodology: A total of eight patients (5 girls, 3 boys) aged between 4 and 16 years were treated with nivolumab at 3mg/kg/dose approximately twice a week in Erciyes University Pediatric Hematology clinic between 2019-2021. Nivolumab treatments of seven patients were given median 11 (4-32) doses and discontinued due to progression at a median 6 months (2-17 months). Results: Four patients were diagnosed with miss match repair syndrome in addition to their malignant disease. Non-Hodgkin lymphoma (two with T-cell and one with histiocyte-rich B-cell) in three patients, brain tumor (pons glioma, midline glioma, glioblastoma multiforme) in three patients, germ cell tumor (yolk salk, immature teratoma) in two patients, one patient had colon adenocarcinoma in addition to brain tumor. Except for nausea in a patient, no drug-related side effect was observed in patients. Conclusion: Nivolumab was well tolerated in patients with CMMRD syndrome with some transient partial responses. There is a risk of developing secondary cancer in patients with CMMRD syndrome. Further studies are needed due to the limited use in children.

Objective: Rhabdoid tumors, which are rare in childhood, are aggressive cancers. It can be particularly seen in 3 different anatomical regions, mostly in the central nervous system, kidneys, and soft tissue in early childhood. In this study, it was aimed to evaluate the clinical, radiological and pathological features of pediatric patients with rhabdoid tumors who were followed up and treated in 3 different pediatric oncology reference centers. Methodology: Erciyes University Faculty of Medicine, Kahramanmaraş Sütçü İmam University Faculty of Medicine, Health Practice and Research Hospital and Adana City Training and Research Hospital, 17 patients diagnosed with rhabdoid tumor between 2002-2021 were retrospectively analyzed. Results: Of the patients, 6 (35%) were female and 11 (65%) were male. Chemotherapy (Doxorubicin, Ifosfamide, Carboplatinum, Etoposide, Vincristine, Actinomycin-D, Cyclophosphamide) was administered to the patients at different times. Radiotherapy was applied to 8 (47%) of the patients. The tumor was in the brain in 8 (47%) of the patients, in the kidney in 4 (23%), in the skin in 4 (23%), and the liver in 1 (6%). Conclusion: In this study, the incidence of rhabdoid tumors was higher in males. This may be due to the small number of cases. The 2 years overall survival rates were 50% in brain tumors, 6% in kidney tumors, and 12% in others, according to tumor localization. The localization and stage of the tumor were determinants of the survival of the patients. More clinical studies are needed to improve survival and identify more effective treatment strategies in these tumors.

Children with constitutional mismatch repair deficiency syndrome (CMMRDS) are prone to different types of cancers. A 16-year-old girl who was misdiagnosed with neurofibromatosis Type-I (NF-I) for 1 years had experienced glioblastoma and colonic adenocarcinoma. After operation, chemotherapy and radiotherapy were started for adenocarcinoma. Genetic analysis from the patient, effected brother, and mother showed heterozygote (c.479 + 36A> G) mutation in the intron 4 region of NF-1 gene. Initially, it was thought that this genetic variant was causative. Furthermore, next generation sequencing showed that the index patient and his brother have homozygote (c.1444 C>T) mutations in the MSH6 gene which are associated with CMMRDS both died because of colonic adenocarcinoma, and T cell non-Hodgkin lymphoma, respectively. Patients with CMMRDS may resemble NF-I. The physicians must not be confused with the previous diagnosis. Increased awareness of CMMRDS, and prompt evaluation for an underlying genetic background is advised if there are unexpected cancer in patients with NF-I.

Background Diabetes and hepatosteatosis are dramatically increasing in childhood. Non-alcoholic fatty liver disease (NAFLD) is defined as a common disorder in adulthood, especially with type-2 diabetes and metabolic syndrome, while very few studies are available on liver health in children with type-1 diabetes. Patients and methods One hundred and ten (52 males and 58 females) patients with type-1 diabetes aged between 8 and 18 years were examined. The lipid profile, liver enzymes and hepatobiliary ultrasound findings of patients were investigated in terms of hepatopathies. Patients diagnosed with fatty liver were evaluated by pediatric gastroenterology specialists for the differential diagnosis and exclusion of other etiologies. The relationships between hepatopathy and age, pubertal status, the duration of diabetes and glycemic control were evaluated. Results Hepatopathy was found in 17 (15.5%) patients. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were normal and did not correlate with the ultrasonography (USG) findings. Hyperechogenicity detected by USG, whether it is true fat or glycogen hepatopathy, was found to be associated with "poor glycemic control" independently of age, puberty status and the duration of diabetes. Conclusions This study contributes to the literature in terms of the relationship between liver health and glycemic control in pediatric type-1 diabetes. Hepatopathies were releated with poor glycemic control independently of the duration of diabetes. This suggested that liver disorders should be considered as one of the subacute complications of diabetes. It was concluded that routine screening for comorbidities and complications in type-1 diabetes should also include hepatobiliary USG, as liver enzymes alone are inadequate for detecting hepatopathies.