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Hepatitis-associated aplastic anemia (HAA) is a form of acquired aplastic anemia (AA) in which bone marrow failure develops after an acute attack of hepatitis. Bone marrow failure leading to AA is generally severe in cases of HAA and fatal if left untreated. This retrospective multicenter study investigated clinical and laboratory characteristics, possible causes, treatment, and outcome of HAA in children. Twenty patients from 8 centers were included in the study. Aspartate aminotransferase and alanine aminotransferase were 10×ULN in 16 patients. Acute liver failure developed in 5 (29%) patients. Pancytopenia was simultaneously present in 6 of 20 (30%) patients. Eleven of the 20 patients (55%) were alive, in remission and transfusion free. Those who were alive either had undergone hematopoietic stem cell transplantation and/or immunosuppressive treatment, except 1 patient who had received no treatment. Patients with the diagnosis of acute hepatitis should be evaluated and followed up carefully for presence of cytopenia, so that definitive treatment of AA can be initiated in a timely and appropriate manner when needed. Copyright r 2021 Wolters Kluwer Health, Inc. 34669357

Aim: Beta-thalassemia major requires regular blood transfusions throughout life, which in turn leads to iron accumulation in the body. While cardiac T2* MRI is the gold standard in determining cardiac iron accumulation, it is not always feasible, which has led to the search for new biomarkers. Herein, the value of growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide in predicting cardiac iron accumulation is investigated in asymptomatic children with beta-thalassemia major. Materials and method: Forty-one patients aged 11–21 years and 41 age-, gender-, body mass index-matched healthy controls were included. Serum growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide levels were compared between the patients and controls. Additionally, the relations of these biomarkers with cardiac and liver T2 * MRI were investigated in the patients. Results: In the patients, growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide levels were higher than healthy controls (p < 0.001, p = 0.025, p < 0.001, respectively). There were no significant correlations of growth differentiation factor-15 and N-terminal pro-B-type natriuretic peptide levels with both cardiac and liver T2 * MRI measurements. While there was no significant correlation of serum galectin-3 with cardiac T2 * MRI measurements, a negative correlation was found with liver T2 * MRI measurements (p = 0.040, rho = –0.325). Conclusion: All three biomarkers investigated in this study failed to predict myocardial iron accumulation in asymptomatic children with beta-thalassemia major. However, a weak relation between serum galectin-3 level and hepatic iron accumulation was demonstrated.

Although survival rates are increasing in acute leukaemias today, this rate is lower in developing countries; there are very few studies conducted on this matter in refugee patients. This research aims to evaluate the survival rate in pediatric Syrian refugee patients with acute leukaemia and compare it with Turkish pediatric leukaemia patients. A total of 144 patients diagnosed with acute leukaemia were included in the study, and their files were reviewed retrospectively. Nineteen 144 patients (13%) were Syrian refugees, and 125 (87%) were Turkish patients. The median age of the Syrian refugees and Turkish patients was 6.9 years (range 1-18 years) and 7.2 years (range 2-18 years), respectively, and gender distribution was similar for both groups (p:0.32). The relapse rate and rate of patients in the high-risk leukaemia group were higher in the Syrian refugee patient group (p=0.05). The survival rates of the Syrian refugee patients at the 11th month and 23nd month of the follow-up were 87.5% and 70%, respectively. The survival rates of the Turkish patients in the 23rd month and 44th month of the follow-up were 96.6% and 85%, respectively. The survival rates of the Turkish patients were significantly higher (p

Objective This study aims to evaluate the demographic information, clinical and laboratory findings of patients with glucose 6 phosphate dehydrogenase deficiency. Material and methods We collected data by reviewing files and electronic records of 65 patients with glucose 6 phosphate dehydrogenase deficiency under the age of 18 years who were followed up in our clinic between 2007 and 2019. Demographic, clinical, and laboratory features, family history, complications of the disease, and history of splenectomy and cholecystectomy were evaluated. Mean, standard deviation, and median values were used when descriptive analyses were presented. Results The age of diagnosis ranged between 1-192 months and the median age of diagnosis was two months. Fifty-nine patients (90.7%) were boys and six (9.2%) were girls. The mean value of glucose 6 phosphate dehydrogenase enzyme on admission was 1,9±1,4 U/g of hemoglobin (Hb). Family history was pesent in 40% of patients in whom information was avaliable. The most common presentation was prolonged jaundice and the most common physical finding was jaundice. Splenomegaly was detected in none of the patients. Cholelithiasis was present in one of 21 patients who were evaluated with ultrasonography. None of the patients required splenectomy, cholecystectomy, and regular erythrocyte transfusion during follow-up. Conclusion As G6PD variants with chronic hemolysis are not usually seen in Turkey, patients who required splenectomy, cholecystectomy, and regular erythrocyte transfusion were not detected. Although glucose 6 phosphate dehydrogenase deficiency is more common in males, it can also be seen in girls. In Turkey, glucose 6 phosphate dehydrogenase deficiency should be considered in patients presenting with prolonged jaundice.

Objective: The aim of this study was to evaluate the demographics, clinical, and laboratory findings and treatment responses of patients with hereditary spherocytosis (HS). Materials and Methods: Data of children with HS were examined. Diagnosis was based on clinical history, physical examination, family history, presence of spherocytes on peripheral blood smear, and osmotic fragility test. Results: A total of 101 patients were included. The median (range) age at diagnosis was 38.0 (1 to 188) months. Mild, moderate, and severe forms of HS were present in 29 (28.7%), 15 (14.9%), and 57 (56.4%) patients, respectively. Family history was available in 73 patients and 56 of these (76.7%) had a positive family history for HS. Forty-five (44.5%) patients needed regular transfusions and all of these had severe disease. Although most patients did not require transfusion postsplenectomy, 2 of 45 (4.4%) patients continued to require transfusion. Transfusion dependence was significantly (P

ObjectivesPaediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.DesignA multicentre, international, collaborative cohort study.Setting91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.ParticipantsPatients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.Main outcome measureAll-cause mortality at 30 days and 90 days.Results1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (pConclusionsThe COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally.

Objective: Prophylaxis is the gold standard in patients with severe hemophilia. In recent years, personalisation of prophylaxis treatment according to pharmacokinetic properties has been used in treatment. In this study, personalisation treatment experience based on the pharmacokinetic dosing tool my-PKfit results in pediatric and adult patients from three centers is shared. Material and Methods: myPKfit (www1.mypkfit.com) was used to evaluate pharmacokinetic parameters in hemophilia A patients receiving recombinant Factor VIII (Takeda Advate ®) prophylaxis. 75 samples in 34 patients (3 samples in 7 patients, 2 samples in 27 patients) were analysed for pharmacokinetic evaluation. Age, weight and baseline FVIII level of the patients were recorded. Pharmacokinetic curves were obtained after entering sampling times, factor dose and sample results. The annual bleeding rate (ABR) of the patients were evaluated before and after the changes made after the pharmacokinetic evaluation. Results: The median age of 34 patients with severe hemophilia A without inhibitors was 12.3±8.7 (1.5-37) years, and the mean weight was 40.0±22.0 (10-83) kg. All patients had a baseline FVIII level of less than or equal to 2 IU/dl. All patients were receiving primary or secondary/tertiary prophylaxis. The mean half-life of the factors of the patients was 9.6±1.4 (7.0-13.4) hours, and the mean time reached below 1 IU/dl was 48.9±11.2 (16.0-77.0) hours. Prophylactic factor therapy was changed in 17 patients after myPKfit, dose increased in 9 patients, the frequency increased in 6 patients, and both dose and frequency increased in 2 patients. With a mean follow-up period of 23.7 +16 (2-49) months, in 17 patients whose prophylaxis regimen was changed after the PK evaluation by myPkyfit, ABR was found to be significantly lower in the post-change period, compared to the last one year before the change of regimen (2.94 + 2.19 and 0.58 + 1.00 respectively) P: 0.028. Discussion: A pharmacokinetic study by the Bayesian method is an increasingly used method for personalised prophylaxis regimen. We believe that myPKfit is beneficial in providing effective and appropriate prophylaxis.

Aim: This study aimed to evaluate the role of real-time three-dimensional (four-dimensional) and speckle tracking echocardiography for early detection of left ventricular systolic dysfunction and also for the relationship between myocardial deformation parameters and myocardial iron load which is measured by cardiac magnetic resonance relaxation time T2* values in asymptomatic children with beta-thalassemia major. Material and Methods: This multicenter cross-sectional study included 40 patients (mean age 15.4 ± 2.9, 42.1% male) and 40 healthy children whose age, gender, and body mass index-matched with patients. Each participant underwent conventional echocardiography and tissue Doppler imaging. Left ventricular ejection fraction; global longitudinal, circumferential, radial strains; twist; and torsion were measured by real-time three-dimensional and speckle tracking echocardiography. Cardiac magnetic resonance imaging T2* was measured in patients. Results: Left ventricular global longitudinal, circumferential, and radial strains were decreased despite preserved global ventricular function in patients compared to healthy children (p = p =.029, p = p

IntroductionChildhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality.MethodsProspective cohort study in 109 institutions in 41 countries. Inclusion criteria: children ResultsAll-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3–11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); pConclusionsChildren with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer.

This study was organized to determine the efficacy and safety of deferasirox (DFX) in reducing the SF of patients with transfusion-dependent thalassemia (TDT). This is a retrospective, descriptive study of 101 transfusion- dependent patients with thalassemia major who were followed for 48 months. Twenty-nine patients who used an alternative chelator either alone or combined, who were not compliant to the treatment, changed the drug due to adverse reactions, and had multiple transfusions and did not complete 4 years of DFX use were excluded. A total 72 out of 101 patients completed the study. SF decreases were noted for the 6-12 and18-year age groups, from a median of 1532 ng/mL to 1190 ng/mL, and from 1386 ng/mL to 1165 ng/mL, respectively (p 0.05). The proportion of patients with SF concentrations2000 ng/mL is decreased (29% at baseline decreased to 15% at the end of the study) during the 48 months. The median SF of those who used30 mg/kg/day (n = 38) increased from 767 ng/mL to 1006 ng/mL, whereas the30 mg/kg/day (n = 34) group's SF concentrations decreased from a median of 1575 ng/mL to 1209 ng/mL (p = 0.029). The decrease of median SF values for Syrian patients was statistically significant (p = 0.043). Most common adverse events were gastric irritation symptoms (19.4%). The total DFX discontinuation ratio was calculated as 9.7%. Although dosages between 25-30 mg/kg/day are adequate to stabilize SF concentrations higher dosages are needed to achieve a statistically significant decrease.

WOS:000614296900001 PMID: 33538100 Adults with cancer are reported to have a higher risk for coronavirus disease (COVID-19) infection and more severe disease and mortality than the general population.1,2 Although children seem to be at a lower risk for COVID-19 than adults,3–5 data specifically addressing children with cancer are limited

Introduction: The lymphoid enhancer factor 1 (LEF1) is a DNA-binding transcription factor that functions in the Wnt signaling pathway. Increased LEF1 activity is associated with progression of several types of cancer including leukemia. Here, we investigated LEF1 isoform expression and genomic variations in acute lymphoblastic leukemia (ALL). Methods: LEF1 isoform expression was evaluated by quantitative real-time PCR in 87 newly diagnosed childhood ALL patients and controls. Moreover, Western blot analysis was performed for detection of LEF1 expression and the hotspot region of LEF1 was screened by deep sequencing. Results: The LEF1 mRNA expression of B cell ALL patients was higher than the controls (LEF1-total P = .011, LEF1-long P = .026). Moreover, B-ALL samples showing higher total LEF1 expression had significantly shorter relapse-free survival (P = .008) and overall survival (P = .011). Although full-length LEF1 expression was similar to the controls in T-ALL, 50% (n = 15) of the ALL patients had increased full-length LEF1 protein expression. Imbalance between short- and full-length LEF1 isoforms may lead to cell survival in ALL. Beside the LEF1 activation, LEF1 gene variations were rarely observed in our cohort. Conclusion: The results indicate that the Wnt pathway may have a pathogenic function in a group of ALL patients and high LEF1-total expression might be a marker for shorter relapse-free survival time in B cell ALL. WOS:000639287900001 33844466 Q3

Background Burkitt leukemia (BL) with the precursor B-cell immunophenotype is a rarely reported condition. The prognosis of such patients is similar to that of classic BL. However, the combination of chromosomal translocations associated with bcl-2 and c-myc rearrangement has a poor prognosis. Observations An 11-year-old child presented with fever and weakness. Bone marrow aspiration showed morphologically L1 type blasts and flow cytometry analysis was compatible with precursor B-cell immunophenotype. Cytogenetic analysis revealed a combination of t(8;14) and t(14;l8). Conclusions The combination of t(8;14) and t(14;l8) can exhibit different immunophenotypical and morphologic features in leukemias.

Although, oral replacement for vitamin B12 deficiency has been proved to be effective in adults, it is mainly treated with parenteral therapy. There are only few studies on oral replacement therapy of vitamin B12 with children. Therefore, we aimed to compare the efficacy of oral treatment with intramuscular vitamin B12 injections in pediatric population.Children with serum cobalamin concentrations less than 300 pg/mL, were treated either with the parenteral therapy or with oral vitamin B12. The primary and secondary outcomes of the study were the normalization of serum vitamin B12 and hemoglobin at first month, respectively.Post-treatment vitamin B12 values were significantly higher than pre-treatment values (p-value.001). Vitamin B12 increased from 183.5 ± 47 pg/mL to 482 ± 318.9 pg/mL in the oral and from 175.5 ± 42.5 pg/mL to 838 ± 547 pg/mL in the parenteral treatment arm (p-value.001). Before treatment, 82 children had anemia according to age and gender. After treatment, 14/41 and 8/41 patients still had anemia at the first month of treatment in the parenteral and oral arms, respectively. The number of patients who still have anemia at the end of the 1st month of treatment did not significantly changed in the parenteral and oral treatment groups (p-value = .44).In this study, both oral and parenteral formulations were shown to be effective in normalizing vitamin B12 levels. We suggest that oral formulations may be considered to be safe as a first line treatment for vitamin B12 deficiency in children.

Standard treatment of vitamin B12 deficiency has not been well established in childhood, the ideal amount of supplemental vitamin B12 is not clear. Vitamin B12 deficiency is classically treated with intramuscular injections. In this study, we aimed to investigate the efficacy of oral therapy in children with vitamin B12 deficiency. Patients with serum cobalamin concentrations

Informed Consent: Written informed consent was obtained from patients’ parents who participated in this case. Peer-review: Externally peer-reviewed. Author Contributions: Literature Review - G.N.O.; Writer - G.N.O., E.C.; / Critical Review - Y.T., H.C., T.C.; Other - G.T. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study has received no financial support.

Aim Children with cancer receiving intensive chemotherapy require multiple transfusions and are at increased risk for blood transmittable diseases such as hepatitis B virus (HBV), hepatitis C virus (HBC), and HIV infections. The aim of this study was to investigate the seroprevalence of HBV, HCV, and HIV in children with cancer and to compare the results with findings in our previous cancer studies conducted before the national free HBV vaccination and the HCV screening program in blood banks were established. Material and methods Sera from 100 children (51 females, 49 males) with cancer treated between January 2010 and January 2012 who received multiple transfusions were investigated for hepatitis B surface antigen (HBsAg), anti-HBs, anti-HCV, anti-HIV at diagnosis and at the end of treatment. Patients were born after 1998 when the national free hepatitis B vaccination program began. Results HBsAg, anti-HCV, and anti-HIV seropositivities were 0% at diagnosis and at the end of treatment. Anti-HBs seropositivity was 58% at diagnosis and 42% at the end of treatment. HBsAg seropositivity, which was 0% at the end of treatment, was lower than 10% during 1994-95, and 40% from 1986 to 1989. Anti-HCV was 0% in contrast to 14% between 1994 and 1995. Seventeen patients with anti-HBs seropositivity at diagnosis were found to be seronegative after intensive chemotherapy. Conclusion The nil seroprevalence of anti-HBsAg, anti-HCV, and anti-HIV in this cohort of children with cancer is encouraging. This progress is due to advances in donor screening techniques in blood banks, good hygenic practices, and the national free hepatitis B vaccination program in Turkey.

WOS: 000478208700001, PubMed ID: 31321910, Background Severe congenital neutropenia is a rare disease, and autosomal dominantly inherited ELANE mutation is the most frequently observed genetic defect in the registries from North America and Western Europe. However, in eastern countries where consanguineous marriages are common, autosomal recessive forms might be more frequent. Method Two hundred and sixteen patients with severe congenital neutropenia from 28 different pediatric centers in Turkey were registered. Results The most frequently observed mutation was HAX1 mutation (n = 78, 36.1%). A heterozygous ELANE mutation was detected in 29 patients (13.4%) in our cohort. Biallelic mutations of G6PC3 (n = 9, 4.3%), CSF3R (n = 6, 2.9%), and JAGN1 (n = 2, 1%) were also observed. Granulocyte colony-stimulating factor treatment was given to 174 patients (80.6%). Two patients died with infectious complications, and five patients developed myelodysplastic syndrome/acute myeloblastic leukemia. The mean (+/- mean standard error) follow-up period was 129.7 +/- 76.3 months, and overall survival was 96.8% (CI, 94.4-99.1%) at the age of 15 years. In Turkey, severe congenital neutropenia mostly resulted from the p W44X mutation in the HAX1 gene. Conclusion In Turkey, mutation analysis should be started with HAX1, and if this is negative, ELANE and G6PC3 should be checked. Because of the very high percentage of consanguineous marriage, rare mutations should be tested in patients with a negative mutation screen., Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK); Turkish Pediatric Hematology Association, This study was supported by Scientific and Technological Research Council of Turkey (TUBITAK) and the Turkish Pediatric Hematology Association.

Lymphomas are solid tumors characterized by the malignant proliferation of lymphoid cells. Neurologic signs encountered in patients with Hodgkin's lymphoma can be due to the direct spread of tumor to the nervous system, secondary to chemotherapy or radiation, secondary to tumor mass compression, infectious causes and paraneoplastic syndromes. Paraneoplastic neurologic syndromes are rarely encountered in patients with Hodgkin's lymphoma and non-Hodgkin's lymphoma. Except for paraneoplastic cerebellar degeneration in Hodgkin's lymphoma and dermato/polymyositis in both Hodgkin's lymphoma and non-Hodgkin's lymphoma, other paraneoplastic syndromes are uncommon and have only been reported as isolated case reports or short series. Here, we present a patient with Hodgkin's lymphoma with symptoms of bilateral lower extremity weakness and loss of sensation before the start of therapy, who was eventually diagnosed as having motor and sensory axonal neuropathy.

Introduction: Paroxysmal nocturnal hemoglobinuria(PNH) in the classical hemolytic form is rare among childhood and children may present with aplastic anemia (AA) phenotype or with an overlapping phenotype of both aplastic and hemolytic components. In the recent years the introduction of FLAER methods prompted a more accurate determination of PNH clones in the suspected patients. Among the patients with aplastic anemia, PNH clone positivity has been detected in 18-59% of these patients with more sensitive FLAER methods. There is limited data related to the effect of PNH clone positivity on treatment outcomes in pediatric AA. Methods: A total of 142 patients, who were diagnosed with acquired AA, from 12 centers were included. All of the patients were tested for PNH clone positivity with either CD55/CD59, FLAER. None of the patients were DEB positive. Results: PNH clone was tested initially at diagnosis with CD55/CD59 flow cytometric analyses in 64 (45%) of the ppatients 66 received IST.atients and with FLAER method in 78 (55%) of the patients. Thirthy three (23.2%) were found to be PNH clone positive, two of them were negative with CD55/CD59 at diagnosis, but were found positive with FLAER during follow-up.Of the PNH clone positive patients 71% were male, compared to 43% in PNH clone nnegative group (p=0.001). The mean ages of patients in PNH clone positive and negative groups were 146±50 vs 121±53 months, respectively(p=0.016). There was no statistically significant difference between clone postive and negative patients in terms of mean Hb, WBC, platelet, AST, ALT, indirect bilirubin and haptoglobin levels measured at diagnosis of AA. However serum creatinin level was significantly higher at diagnosis in PNH clone postive patients compared to negative patients (0.57±0.18 vs 0.49±0.15 mg/dl); whereas MCV levels were significantly higher in clone postive group (93.2±9.7 vs 87±11.5 fl). Of 33 patients with PNH clone positivity, 19 (57.6%) were treated with immunosuppressive treatment (IST), as first line treatment, whereas of the clone negative 109 patients, 66 received IST (60.6%) (p=0.76). Of the 19 clone postive patients 11 (57.9%) had treatment response; whereas 36/65 (55.4%) of clone negative patients responded to IST. There was no statistically significant difference between PNH clone positive and negative groups in terms of IST response. IST response was not affected according to gender, age, ALT, AST, WBC, Hb, thrombocyte count, size of the erythrocyte and granulocyte clone at diagnosis. Thrombosis developed in 2 of clone positive (6.1%) and 2 of clone gative patients (1.8%) (p=0.23). Three year survival was 97.6±2.4% and 37.2±8.7% among IST responders and IST non-responders, respectively (p=0.0). Of the 142 patients, 59 underwent HSCT, five received eculizimab and 1 received eltrombopag treatments. Three patients developed clonality during follow-up. Thirty-seven (26%) of the patients deceased among the all study group and the causes of mortality were fungal infection, sepsis, pneumonia, leukemia progression, HSCT related complications, thrombosis and bleeding. Conclusions: PNH clone positivity was found in 23.2% of our patients with pediatric acquired AA. We found no impact of clone positivity on outcome in terms of IST response. This is one of the largest cohort of pediatric patients which investigated the impact of PNH clone positivity on AA outcome. Disclosures No relevant conflicts of interest to declare.

Informed Consent: Written informed consent was obtained from patient’s parents. Peer-review: Externally peer-reviewed. Author Contributions: Concept - G.N.O.; Design - T.C.; Supervision -T.C.; Funding - G.T.; Materials - G.T.; Data Collection and/or Processing - G.T.; Analysis and/or Interpretation - G.T., G.N.O.; Literature Review - G.N.O., G.T.; Writer - G.T.; Critical Review - T.C., G.N.O. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study has received no financial support.

Aim: The aim of this study was to evaluate the demographic information, clinical and hematologic findings and treatment response of patients diagnosed with hereditary hemolytic anemias other than thalassemia at a single center. Materials and Methods: A total of 157 children with a diagnosis of hereditary hemolytic anemia except thalassemia were included. Patients' files were reviewed retrospectively. Demographic, clinical and laboratory characteristics, family history, complications, history of splenectomy and cholecystectomy, splenectomy response, use of chelating agents and other treatments, first transfusion age and transfusion frequency of patients were evaluated. Mean, standard deviation, median and 25-75 percentile values were used when descriptive analysis were presented. Mann Whitney U and Kruskal Wallis Tests were used for nonparametric groups. Pearson Chi Square and Fisher Tests were used when categorical comparisons were made. A value of P Results: Of the 157 patients , 101 patients (64,3%) had hereditary spherocytosis, 39 patients had (24,8%) glucose-6 phosphate dehydrogenase deficiency (G6PD), 15 patients had (9,6%) sickle cell anemia and 2 patients had (1.3%) pyruvate kinase deficiency. Sixty-one patients (38,9%) were girls and 96 were boys (61,1%). Median age of diagnosis was 10 months (range 1-188 months). Of 97 patients whom family history was questioned, 63 (64.9%) had family history. Most common complaint at diagnosis was paleness. Eighty-two patients had splenomegaly. Twenty-two patients (14%) had cholecystectomy and 56 patients (35.7%) had splenectomy on follow-up. The most frequent indication for splenectomy was hereditary spherocytosis. Fifty-eight (36.9%) patients required regular transfusion. Mean ferritin level of all was 506.3±1175.0. Patients with pyruvate kinase had the highest ferritin levels. Erythropoietin was used for 1 patient with hereditary spherocytosis in infancy without a response. Ten of 15 patients with sickle cell anemia were using hydroxyurea. Thirteen percent of all were using chelating agents. Conclusion: Hereditary spherocytosis and G6PD deficiency were the most common hereditary hemolytic anemias except thalassemia in our center. Family history was more frequent in hereditary spherocytosis compared to other hereditary hemolytic anemias. Patients with G6PD deficiency were diagnosed earlier than other hereditary hemolytic anemias. Hereditary spherocytosis was the most common indication for splenectomy and eliminated/decreased transfusion requirement in 96%. Patients with other hemolytic anemias had lower iron load compared to thalassemia except pyruvate kinase deficiency patients. Disclosures No relevant conflicts of interest to declare.

Bilateral Congenital cystic adrenal neuroblastoma (NB) with cystic liver metastases is a very rare condition and only few cases have been reported in the literature. Herein we report a case of a congenital bilateral cystic adrenal NB with cystic liver metastases and briefly discuss characteristic imaging features of cystic NB.

58th Annual Meeting and Exposition of the American-Society-of-Hematology (ASH) -- DEC 03-06, 2016 -- San Diego, CA, WOS: 000394452701110, Amer Soc Hematol, TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK), Yilmaz Karapinar: TUBITAK: Research Funding.

Thiamine is a water-soluble vitamin. Thiamine deficiency can present as a central nervous system disorder known as Wernicke’s encephalopathy, which classically manifests as confusion, ataxia, and ophthalmoplegia. Wernicke’s encephalopathy has rarely been reported following hematopoietic stem cell transplantation. Herein, we report Wernicke’s encephalopathy in a patient with acute myeloid leukemia who had been receiving prolonged total parenteral nutrition after haploidentical allogeneic hematopoietic stem cell transplantation. To the best of our knowledge, this is the first case reported from Turkey in the literature.

Cocukluk cagi kanserleri sagkalim oranlarinin artmasi ile dikkatler tedaviye bagli gec yan etkiler uzerinde yogunlasmaya baslamistir Kanser tedavisinin en onemli komplikasyonlarindan biri de ikincil kanserlerdir Cocukluk caginda kanser geciren olgularda ikincil malinitelerin riski 2 3 kat daha fazladir ve 20 yilda 3 2 olarak bildirilmistir Bu yazida kanserden kurtulmus cocuk hastalarda ikincil kanser olusumundaki risk etmenleri kanser tipine ve tedavi sekline gore farkliliklari ile hastalarin takibindeki ozellikler irdelenmistir Turk Ped Arfl 2011; 46: 270 4

Amac: Sunnet cocuklarda en sik uygulanan cerrahi girisimlerden biridir ancak kanama bozuklugu olan cocuklarda sunnetle ilgili az sayida calisma vardir Bu calismada kanama sorunu olan cocuklarda sunnetle ilgili deneyimlerimizi paylasmayi amacladik Gerec ve Yontem: Cerrahpasa Tip Fakultesi Cocuk Hematoloji Bolumu rsquo;muzde kanama bozuklugu nedeni ile izlenen ve Cerrahpasa Tip Fakultesi Cocuk Cerrahisi Bolumu rsquo; rsquo;nde 2000 2010 yillari arasinda sunnet yapilan 18 olgunun yaslari 3 14 dosyalari geriye donuk olarak incelendi Tedavi yontemleri komplikasyonlar ve sonuclar degerlendirildi Bulgular: Olgularin yedisinde hemostazin birinci evresini ilgilendiren sorun vardi: Ucu Glanzmann trombastenisi ikisi Bernard Soulier sendromu ikisi kronik immun trombositopenik purpura idi Diger 11 olgu ise hemostazin ikinci evresini ilgilendiren nedenlerle izlemde olan olgulardi: Uc von Willebrand hastaligi vWH bir faktor V eksikligi bir hemofili B ve ikisi inhibitorlu olan alti hemofili A hastasi Trombosit sayi ve veya islev bozuklugu olan hastalarin hicbirine trombosit verilmedi Sadece antifibrinolitik ve yerel fibrin yapistiricilarla islem sorunsuz olarak gerceklestirildi ve kanama olmadi Hemofili inhibitorsuz ve vWH olan olgularda ise sunnet oncesinden baslatilan 2 3 faktor 15 25 kg gun tedavisine sunnetten sonra 24 48 saat devam edildi Antifibrinolitik tedavisi ve fibrin yapistirici da kullanilarak hicbir hastada kanama gorulmedi Iki dusuk duzeyde inhibitorlu olguda yogun ldquo;bypas rdquo; ajanlari kullanildi 12 ve 18 gun sure ile Kanama ancak rFVIIa ve aPCC rsquo;nin ardisik kullanimi ile durdurulabildi Cikarimlar: Kanama bozuklugu olan cocuklar deneyimli bir merkezde guvenle sunnet edilebilirler Kanama bozuklugu olan cocuklarin sunnetinde antifibrinolitik ve yerel hemostatik maddelerin kullanimi ile hemofilik hastalarin faktor dozlari azaltilabilir ve trombosit bozuklugu olan hastalarda trombosit transfuzyonundan kacinilabilinir Turk Ped Arfl 2011; 46: 313 7

Aim: The aim of the study is to evaluate the efficacy, complications and long term results of splenectomy in children with hematologic diseases. Patients and Methods: This study includes retrospective analysis of the medical records of 158 children between 0-18 years old who underwent splenectomy due to hematologic diseases from 1989 to 2017. Gender, splenectomy indications, age of diagnosis, splenectomy age, vaccination status, splenectomy outcomes, complications and mortality were evaluated. Results: Of the cases, 88 (55.7%) were female and 70 were male (44.3%). Indications for splenectomy were hereditary spherocytosis in 59 (37.3%), immune thrombocytopenia (ITP) in 50 (31.6%) and thalassemia major in 40 (25.3%) children. The median age of diagnosis was 3.9 years, the median splenectomy age was 9.2 years, the median time from diagnosis to splenectomy was 5.3 years in all cohort. Mean follow-up time of patients after splenectomy was 7.3±5.2 years. All patients except one were immunized before splenectomy. Responses were assessed based on standart criteria for each disease. Response was seen in 94.7% of patients with hereditary spherocytosis and 80% of ITP patients. Twenty-two percent of splenectomised children with thalassemia major had a decrease in transfusion frequency. Infections following splenectomy were reported in 22.8%. One patient had thrombosis related to splenectomy, none of the cases had major bleeding. There was no death due to sepsis. One patient with ITP died due to Subacute Sclerosing Panencephilitis (SSPE). Conclusion: Splecetomy is associated with good remission rates following ITP and hereditary spherocytosis. Splenectomy should be performed only in selected cases with transfusion dependent thalassemia. Post-splenectomy sepsis is uncommon. Future studies should focus on health quality of life and cost analysis of splenectomy in children. Disclosures No relevant conflicts of interest to declare.

Dear Editor, Hemophilia B is a X-linked recessive bleeding disorder which occurs as a result of Factor IX (FIX) deficiency (1, 2). In some patients with hemophilia, antibody (inhibitor) and allergic reaction may develop against FIX protein which is administered for treatment (3). While antibody develops against the factor administered in approximately 15–25% of the patients with severe hemophilia A, this rate is much lower in patients with hemophilia B (3%). Life-threatening allergic reactions may develop in 50% of the patients who have inhibitor (4). There is no efficient treatment which can be used to prevent allergic reaction developing secondary to antibody response. In this case report, the difficulties in treatment of an infant with severe hemophilia B who developed antibody and allergic reaction against FIX treatment have been discussed. Our patient was diagnosed with hemophilia B after investigations performed because of severe hemorrhage which developed following circumscision at the age of five months. At presentation, the bleeding tests revealed an activated partial thromboplastin time (aPTT) of 104 seconds and a FIX level of 1%. A concentrate containing FIX protein obtained from 9 doses of plasma was used to stop bleeding. When the patient was 14-month old, he was rehospitalized because of head trauma. His cranial ultrasonography and brain tomography findings were found to be normal. FIX concentrate (Replenine®) was initiated at a dose of 80 IU/kg by way of slow intravenous infusion because of head trauma. However, anaphylactic reaction (diffuse urticaria, blushing in the face, cough, dyspnea, cyanosis) developed during infusion of factor concentrate. Dexamethasone, antihistaminic and adrenaline were administered for treatment. In the following administrations, his treatment was switched to Berinine® which is another FIX concentrate with prophylactic administration of antihistaminic and steroid. A similar anaphylactic reaction developed in the third minute of infusion of this new concentrate and treatment was immediately discontinued. Antihistaminic, dexamethasone and adrenaline were administered again. In the follow-up visit one month later, aPTT was found to be 134 s, the FIX level was found to be 0.1% and the amount of inhibitor was found to be 1.7 BU. As a result of mutation study, CGA>TGA (R252X) mutation was demonstrated in exon 8, n.30875, codon 252. Non-human-derived recombinant active FVIIa (rFVIIa - Novo Seven®) was given for severe bleedings in the following periods because of development of antibody. Allergic reaction may occur against FIX protein in patients with hemophilia B who have developed antibody in contrast to hemophilia A (5). Follow-up and treatment of hemorrhage is difficult in patients with hemophilia who are allergic against external FIX protein and develop FIX-related antibody. Antibodies are involved in morbidity and mortality related with bleeding. FIX concentrates are not appropriate, because these patients develop antibody and allergy against FIX concentrates. Since treatment with active prothrombin complex concentrate (aPCC) involves FIX, it may result in allergic reaction similarly (6). Development of recombinant FVIIa provided an appropriate treatment option for patients with hemophilia who develop inhibitor. However, no consensus has been made in relation with treatment with aPCC and rFVIIa in FIX patients who have developed antibody (7). In our own individual experience, it was observed that hemostasis control was provided with aPCC treatment during surgery in patients with hemophilia B who developed antibody (8). It should be kept in mind that the cost of recombinant FVIIa concentrates is high and they carry a risk of thrombosis. Therefore, inhibitor elimination and desensitization treatment should be considered in these patients (9). Elimination of antibody is considerably difficult and treatment success is poor in patients with hemophilia B who are allergic against Factor IX concentrates and who develop antibody. Immune tolerance induction (ITI) treatment which is commonly used in patients with hemophilia A to eliminate antibody and is successful is generally ineffective in these patients. It is recommended that patients with high-risk in terms of development of antibody (patients with complete gene loss) should be identified with molecular analyses at the time of first diagnosis and monitored closely in the beginning of treatment (5). In patients with hemophilia B, it is recommended that the first 10–20 treatments should be administered in hospital in terms of allergy and family members should be trained in terms of the risk of anaphylaxis (10). In conclusion, we aimed to emphasize the difficulties in follow-up of patients with severe hemophilia B who develop allergic reaction and inhibitor against FIX concentrates. Since life-threatening allergic reactions against Factor IX concentrates may develop, the initial administrations in treatment of patients with newly diagnosed hemophilia B should be definitely performed in hospital environment. Recombinant FVIIa is the only appropriate option for treatment of hemorrhage in these patients. Despite a need for inhibitor elimination and desensitization treatment, there is no current application in this area and further studies are needed.

Olgu On dört yaşında erkek hasta ayaklarda morluk ve diş etlerinde kanama yakınması ile acil servisimize başvurdu Fizik bakısında; karaciğer büyüklüğü yaygın ekimoz ve peteşileri vardı Laboratuvar tetkiklerinde lökosit sayısı 307 800 mm3 hemoglobini 7 9 g dL trombosit sayısı 46 000 mm3 saptandı Periferik yayma ve kemik iliği aspirasyonunda silme blast görüldü Tanı anında merkezi sinir sistemi tutulumu vardı T hücreli akut lenfoblastik lösemi ALL olarak fenotiplendi Translokasyon çalışmalarında; t 9;22 t 4;11 t 12;21 ve t 1;19 negatif bulundu Hasta bu bulgularla orta risk grubuna alındı ve TRALL BFM 2000 protokolü indüksiyon tedavisi başlandı Sekizinci gün periferik yaymada blast görülmedi On beşinci gün kemik iliği aspirasyonunda 4 blast saptandı ancak akım sitometrisi ile değerlendirme sonucu minimal kalıntı hastalık 31 39 normali lt;1x10 4 bulunduğundan hasta yüksek risk grubuna geçirildi Otuz üçüncü gün kemik iliği aspirasyonunda 4 blast belirlendi Hastanın indüksiyon tedavisinin ilk günlerinden itibaren olan sinüs taşikardisi başlangıçta anemisi ile ilişkilendirilmişti ancak hemoglobin değeri transfüzyonlarla normal sınırlarda tutulmasına rağmen aralıklı olarak kalp tepe atımları dinlenirken 100 140 dk arasında bulundu Soygeçmişinde bilinen tiroid hastalığı veya otoimmün bir hastalık yoktu Fizik bakısında üfürümü yoktu periferik nabızları alınıyordu Tiroid muayenesi doğaldı Ateşli nötropeni nedeniyle antibiyotik tedavisi verildi ateşi düştüğü dönemde enfeksiyonu yokken de taşikardisi düzelmedi Elektrokardiyografisinde sinüs taşikardisi dışında özellik belirlenmedi Teleradyografi ekokardiyografi ve kalp enzimlerinde patoloji saptanmadı Tanı: Primer hipertiroidi Tiroid patolojileri açısından tiroid işlev testleri istendi Serbest T3 4 76 pg mL ve serbest T4 2 15 pg mL düzeyleri yüksek TSH düzeyi düşük 0 6 mIU L saptandı Anti tiroglobulin 14 81 IU mL n= 0 40 anti tiroid peroksidaz 7 72 IU mL n= 0 35 ve TSH almaç 0 45 IU mL n= 0 1 1 otoantikorları negatif tiroid ultrasonografisi ve Doppler ultrasonografisi normal olarak saptandı Bu dönemde periferik yayma ve kemik iliği remisyonda olduğundan tiroid ultrasonografisi ve Doppler ultrasonografisinde de patolojik özellik belirlenmediğinden tiroid tutulumu açısından biyopsi yapılması gerekli görülmedi Hasta birincil hipertiroidi olarak değerlendirilerek propranolol ve metimazol tedavilerine başlandı Tedavinin birinci ayında tekrarlanan tiroid işlev testleri normal düzeylerde bulundu İzleminde yakınması tekrarlamadı ve taşikardisi düzeldi., Case A 14 year old male patient presented to our emergency deparment with complaints of bruises on the feet and gingival bleeding Hepatomegaly and diffuse ecyhmoses and petechiae were present on physical examination Laboratory findings were as follows: WBC: 307 800 mm3 hemoglobin: 7 9 g dL platalet count: 46 000 mm3 Abundant blasts were observed on the peripheral smear and bone marrow examination Central nervous system involvement was present at the time of diagnosis Phenotyping revealed a diagnosis of T cell acute lymphoblastic leukemia ALL Translocation studies revealed negative t 9;22 t 4;11 t 12;21 and 1;19 With these findings the patient was classified into the moderate risk group according to the modified BFM 95 risk classification TRALL BFM 2000 protokol induction treatment was started On the 8th day no blast was observed on the peripheral blood smear On the 15th day 4 blast was found on bone marrox examination but the patient was classified into the high risk group since minimal residual disease was found to be 31 39 normal value: lt;1x10 4 as a result of flow cytometry On the 33trd day 4 blast was observed on bone marrow examination Sinus tachycardia observed in the patient from the first days of induction treatment was initially associated with anemia but apical heart rates were intermittantly found to be 100 140 min although hemoglobin values were kept in the normal limits with transfusions Familial history did not include any known thyroid disease or autoimmune disease No murmur was heard and peripheral pulses were palpable on physical examination Thyroid examination was found to be normal Antibiotic treeatment was given because of febrile neutropenia Tachycardia did not resolve in the period when the patients had no fever and infection Electrocardiography did not reveal any pathology except for sinus tachycardia Telecardiography echocardiography and cardiac enzymes were found to be normal Diagnosis: primary hyperthyroidism Thyroid function tests were ordered in terms of thyroid pathology Free T3 4 76 pg ml and free T4 2 15 pg ml levels were found to be high and TSH level was found to be low 0 6 mIU L Anti thyroglobulin 14 81 IU mL n=0 40 anti thyroid peroxidase 7 72 IU mL n=0 35 and TSH receptor 0 45 IU mL n=0 1 1 autoantibodies were found to be negative Thyroid ultrasonography and Doppler ultrasonography were found to be normal Sine the peripheral blood and bone marrow were in remission in this period and no pathology was found on thyroid ultrasonography and Doppler ultrasonography biopsy was not considered necessary in terms of thyroid involvement The patient was evaluated as primary hyperthroidism and propranolol and methimazole treatment was started Thyroid function tests repeated in the first month of treatment were found to be normal His complaint did not recur and tachycardia resolved in the follow up Discussion Acute lymphoblastic leukemia is the cause of approximately 25 30 of childhood cancers and 75 of childhood leukemias Tachycardia may ocur beacuse of different causes during treatment of leukemia Although infection fluid loss and enamia are frequently found as the cause thyroid pthologies should also be considered in the etiology Hyperthroidism is a disease which should be considered primarily in the differential diagnosis of tachycardia in individuals who are healthy otherwise Tachycardia due to increased sympathetic activity is frequently observed in hyperthroidism Different thyroid pathologies amy accompany leukemia; hypothyroidsm and hyperthyroidism due to different causes may be observed in the patients and sick euthyroid syndrome may be found 1 2 3 In the course of severe diseases including leukemia changes in thyroid hormon levels may ocur in the absence of thyroid disease and this is called sick euthyroid syndrome The most commonly observed among these changes is decreased T3 concentration alone or incombination with decreased T4 concentration 2 It is thought that thyroid hormon levels change with the effect of the tumor chemotherapy and impairment in the emotional and physical condition in children with cancer but the mechanism has not been fully elucidated 4 5 These changes in thyroid hormones may be briefly an adaptation of the body to morbidity but the physiological effects of this condition are not known In children the negative effects of low levels of a hormone which has been shown to be important for growth and development and brain development may be observed in the long term In a prospective study performed in children receiving cancer treatment changes in thyroid hormon levels were found in 90 of the patients 1 In this study it was shown that the variable which had the greatest effect on hormon change was dexamethasone treatment It is known that dexamethasone suprsses the release of TSH T3 and prolactin Corticosteroids additionally decrease TBG binding capacity and inhibit peripheral transformation of T4 to T3 6 7 8 Corticosteroids are one of the most important drugs in ALL treatment and are used with high doses for a long period Thyroid involvement can be rarely observed in patients with leukemia 9 10 11 12 Thyroid functions generally do not change but hypothyroidism is observed more frequently and hyperthroidism has been found in some patients It is thought that hyperthroidism develops as a result of rapid release of thyroid hormone into the blood due to destruction of thyroid follicles with malignency Ultrasonography Doppler ultrasonography computarized tomography and fine needle biopsy are recommended in clinically suspicious patients even though thyroid function tests are normal We found primary hyperthroidism in our patient who had unresolved tachycardia from the first days of treatment during leukemia treatment Low thyroid autoantibodies and normal parenchymal appearance on thyroid ultrasonography suggested that autoimmunity was not the cause of hyperthyroidism The fact that the patient was in remission and thyroid Doppler ultrasonographic examination was normal excluded thyroid involvement for the time being Hoever long term follow up of this patient will allow better differential diagnosis for autoimmune thyroiditis or thyroid involvement In this article we aimed to emphasize that hyperthyroidism should be considered as a cause in presence of tachycardia observed during leukemia treatment though it is not a frequent cause and to discuss thyroid pathologies in patients with leukemia References

Amac: Glanzmann trombastenisi nadir gorulen trombosit cokmesindeki bozuklukla seyreden otozomal cekinik gecisli bir hastaliktir Bu calismada Cerrahpasa Tip Fakultesi Cocuk Hematoloji Bolumunde izlenen Glanzmann trombastenili hastalarda tani ve tedavi yaklasimlarimizi sunmak istedik Gerec ve Yontem: On dokuz hasta 42 kiz 58 erkek; ortanca yas: 10 ay geriye donuk olarak degerlendirildi Bulgular: Kanama yakinmalarinin baslama ortanca yasi dokuz ay 2 hafta 24 ay idi Hastalarin tumunde basvuru yakinmasi siradisi cilt ve mukoza kanamasiydi On dort hastada anne baba arasinda akrabalik vardi On bes olguda akim sitometri yapilabildi Buna gore yedisi tip I altisi tip II ve ikisi tip III olarak degerlendirildi Uygulanan dokuz girisimsel islemlerde; trombosit transfuzyonu traneksamik asit rekombinan aktive faktor VII ve fibrin yapistiricinin tek veya birlikte kullanimlari ile hemostaz saglandi hicbir girisimsel islemde ciddi kanama komplikasyonu yasanmadi Cikarimlar: Glanzman trombastenisi olgularinda girisimsel islemler sirasinda kanama kontrolunu saglamak zor olabilir girisimler sirasinda yerel uygulamalar desmopressin steroid ve antifibrinolitik ajanlar tedavi icin yararli olabilir Turk Ped Ars 2012; 47: 104 6