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The prevalence of intracardiac thrombus (ICT) is gradually increasing, though it is rare among children. Data related to the occurrence of ICT among children are limited, and treatment recommendations have been made utilizing adult guidelines. The primary objective of this study is to determine associated factors, management, and outcomes of intracardiac thrombosis in children. Between January 2013 and January 2020, patients diagnosed with ICT at the Pediatric Hematology-Oncology and Pediatric Cardiology departments in our hospital were included in the study. Demographic characteristics, clinical and laboratory findings, treatment protocols, and outcomes were analyzed retrospectively. The median age at diagnosis was 10.5 months (2 days to 14.5 years), and the median follow-up period was 6.5 months (1 month to 3.1 years). The most common primary diagnoses of the patients, in order of frequency, were heart disease (n: 8), metabolic disease (n: 3), prematurity and RDS (n: 3), burns (n: 2), pneumonia (n: 2), and asphyxia (n: 2). CVC was present in 19/23 of the patients. The reasons for CVC insertion were the need for plasmapheresis in one patient with a diagnosis of HUS and the need for well tolerated vascular access because of long-term hospitalization in others. LMWH was administered to all patients as first-line therapy. Complete response was achieved in 19 (79%) of 24 patients and 4 patients (16.6%) were unresponsive to medical treatment. It was found out that the thrombus location, type, sepsis, and hemoculture positivity, as well as the presence of CVC, had no impact on treatment response (chi-square P = 0.16, 0.12, 0.3, 0.49, 0.56). Moreover, no correlation was determined between thrombus size and treatment response (Mann Whitney U test P = 0.47). The mortality rate was determined to be 12.5% (3/24). Spontaneous occurrence of ICT is rare in childhood, without any underlying primary disease or associated factor. The presence of CVC, sepsis, and heart disease are factors associated with ICT. The success rate is increased with medical treatment. There was no significant difference in treatment response between the newborn and 1 month to 18-year-old patient group. It has been demonstrated that thrombus size, type, localization; sepsis, and hemoculture positivity had no impact on the treatment response.

Background SARS-CoV-2, a respiratory viral disease, is thought to have a more severe course in patients with malignancy and low immune systems. Methods This prospective single-center study was conducted at the University of Health Sciences Dr. Behçet Uz Children's Hospital from September 22 and December 31, 2021. Asymptomatic COVID-19 transmission rates were assessed using SARS-CoV-2 serology in patients with leukemia who had no history of COVID-19 infection. Results Among the 54 patients, 19 (35.2%) were females and 35 (64.8%) were males. The median age was 5.5 years (min 6 months, max 17 years). Forty-nine (90.5%) of the leukemia patients had acute lymphoblastic leukemia (ALL), while 5 (9.5%) had acute myeloid leukemia (AML). Five of the 54 patients had a history of COVID-19 or contact with a positive person. SARS-CoV-2 IgG positivity was detected in 18 (36.7%) of 49 patients with no history of COVID-19 infection. Discussion Leukemia patients have a high seroconversion for SARS-CoV-2 without showing any symptoms supporting the asymptomatic course of COVID-19 infection in this risk group.

Vincristine (VCR), which is a key component of chemotherapy, is important for survival. VCR is associated with a well-known side effect, including neurotoxicity. The aim of this study was to evaluate the features of vincristine-induced peripheral neuropathy (VIPN) and the effectiveness of pyridoxine plus pyridostigmine therapy in children with acute lymphoblastic leukemia. The WHO and NCI CTCAE neurotoxicity scorings were used to evaluate VIPN at diagnosis, in the first month, and after the third month of the treatment. The clinical features of 23 patients having acute lymphoblastic leukemia with VIPN during the period of July 2013–February 2016 were prospectively evaluated. The mean age was 72.8 ± 51.6 months, and 26.1%, 56.5%, and 17.4% were in standard, moderate, and high-risk groups, respectively. Neuropathy frequently occurred at induction (82.6%) and reinduction (17.4%) of the protocol. Drop foot (82.6%), leg pain (82.6%), and difficulty in walking (82.6%) were observed. The mean total cumulative dose of neuropathy occurrence was 5.6 ± 2.03 mg/m2. Our study showed that both the WHO and NCI CTCAE scorings were significantly improved via pyridoxine plus pyridostigmine therapy. The WHO and NCI CTCAE scorings may be used for evaluating neuropathy at diagnosis and follow-up of neurotoxicity with treatment. Pyridoxine plus pyridostigmine therapy may be an effective option in the treatment of VIPN.

L-Asparaginase (L-Asp) is a critical component of chemotherapy for acute lymphoblastic leukemia (ALL). However, toxic effects associated with L-Asp, such as hepatic dysfunction, pancreatitis, hypercholesterolemia, and hyperglycemia, have occurred. In addition, acute pancreatitis is a significant life-threatening adverse event associated with ALL. We describe 2 patients with ALL who had L-Asp-associated pancreatitis (AAP), with one patient presenting with hyperglycemia and the other presenting with hypoglycemia during induction treatment. When octreotide was administered to both of these patients, the clinical findings and laboratory data were improved. AAP was not repeated after treatment with pegylated asparaginase. Although AAP has a high risk of mortality and morbidity in childhood, APP treatment with appropriate agents, such as octreotide, can be successful. (C) 2020 Elsevier Inc.

Type II Griscelli Syndrome (GS) is caused by a mutation in the RAB27A gene and usually manifests with silvery-gray hair, immune deficiency and the development of hemophagocytic lymphohistiocytosis (HLH). A hematopoietic stem cell transplantation is the curative treatment for HLH and reduced-intensity conditioning prevents the morbidity/mortality in the transplantation related to myeloablative conditioning. We report on a 21-month old boy with cerebral involvement of HLH related to GS.

Background Acute viral respiratory infections are common causes of febrile episodes in children. There are still limited data about distribution of acute viral respiratory infections in children with cancer. Objective The first aim of this study was to evaluate the viral etiology and seasonality of acute viral respiratory infection in pediatric patients with cancer in a 3-year study. Our second aim was to evaluate the impact of viral infections on delaying the patients' chemotherapy or radiotherapy. Materials and methods This cross-sectional study was conducted from January 2014 to July 2017. Nasopharyngeal aspirates were analyzed in patients younger than 21 years with acute respiratory infections. Patients were treated in the Pediatric Hematology and Oncology Department of Dr. Behcet Uz Children's Hospital with real-time multiplex polymerase chain reaction. Data were analyzed to determine the frequency and seasonality of infections. The χ or the Fisher exact tests were used. Results A total of 219 samples of nasopharyngeal aspirates and blood were analyzed. The mean patient age was 76.8±59.3 months, with 46.3% female and 53.7% male children in a total of 108 patients. Of this total, 55% (60/108 cases) had multiple acute respiratory infections. Acute lymphoblastic leukemia (48.1%) was the most prevalent disease. The 3 most prevalent viruses were human rhinovirus (HRV) (33.1%), parainfluenza (PI) (18.7%), and coronavirus (CoV) (14.8%). In terms of the seasonal distribution of viruses, PI was most common in winter 2014, HRV in spring 2014, HRV in fall 2014, PI in winter 2015 and summer 2015, CoV in spring 2015, HRV in fall 2015, both influenza and HRV in winter 2016, both human metapneumovirus and bocavirus in spring 2016, HRV in summer 2016, both HRV and PI in fall 2016, both respiratory syncytial virus and influenza in winter 2017, HRV in spring 2017, and both HRV and adenovirus in summer 2017. The mean duration of neutropenia for patients with viral respiratory infection was 17.1±13.8 (range: 2 to 90) days. The mean duration of symptoms of viral respiratory infection was 6.8±4.2 (range: 2 to 31) days. A delay in chemotherapy treatment owing to viral respiratory infection was detected in 73 (33.3%) patients. The mean duration of delay in chemotherapy treatment was 9.6±5.4 (range: 3 to 31) days. Conclusions In conclusion, we report our 3-year experience about the frequency and seasonality of respiratory viruses in children with cancer.

BACKGROUND Candidemia and Candida-associated catheter-related bloodstream infections (CRBSIs) are the significant cause of mortality and morbidity in patients with malignancy. METHODS A retrospective analysis including all pediatric hematologic/oncologic malignancies patients with CRBSIs treated in Dr. Behcet Uz Children Diseases and Surgery Training and Research Hospital between the period of 2009 and 2020. RESULTS During the study period, 53 children with CRBSIs associated with Candida species were included. The most common malignancy was acute lymphoblastic leukemia (45.3%) and acute myeloid leukemia (15.1%). A total of 56 Candida isolates were present including non-albicans Candida species (80.4%) and Candida albicans (19.6%). The most common isolated Candida species was Candida parapsilosis (42.9%) and followed by C. albicans (19.6%). The ratio of azole prophylaxis was significantly higher in patients with the non-albicans Candida group (P=0.031). Candida-related endocarditis (vegetation) was present in 2 (3.8%) patients, and the overall rate of hepatosplenic candidiasis was 3.8%. Seven days Candida attributable mortality was 7.5% (4 patients) and 30 days Candida attributable mortality was 11.3% (6 patients). The Candida species responsible for the Candida-related deaths were as following: Candida tropicalis (n=3), C. parapsilosis (n=2), and C. lusitanae (n=1). CONCLUSION In pediatric cancer patients with Candida-associated CRBSIs, evaluation of the patient for organ involvement including liver and spleen ultrasonography and cardiac involvement with echocardiography are essential regardless of the patients' clinical picture.

Objective: Anthracyclines which are the main drug of chemotherapy protocols had cardiotoxicity as the most frequent and well-known side effect. We aimed to evaluate prospectively the heart rate variability with 24-hour Holter electrocardiography (ECG) in children with cancer who treated with anthracycline drugs. Material and Methods: The 24-hour Holter ECG monitoring was performed at the baseline, at time of 120 mg/m2 and ≥240 mg/m2 of cumulative anthracycline dose in patients with cancer who treated with anthracycline. The time-domain and frequency-domain measurements of heart rate variability (HRV) were obtained. The patients were classified into three groups as Group1:at baseline (n=54), Group 2:≥120mg/m2 (n=54), Group 3:≥240mg/m2 (n=54).Results: The median age was 48 months (range 9-192 months). All types of cancer were 38 patients (70.4%) of acute leukemia, two patients (3.8%) of T lymphoblastic lymphoma, and 14patients (25.8%) of other childhood cancer who treated with anthracycline. However, all heart rate variability parameters were decreased after each increased cumulative anthracycline dose, especially time-domain parameters such as nSDNN index, rMSSD, pNN50, frequency parameters such as LF, HF, and Total power were significantly altered among Group1 and Group 3. LF/HF ratio was also statistically significantly increased in Group 3. According the heart rate parameters, the mean average heart rate, mean minimum heart rate and mean RR were statistically significantly prolonged from Group1 to Group 3.Conclusion: Heart rate variability parameters are a noninvasive technique to demonstrate cardiac autonomic neural dysfunction and early myocardial injury. The 24-hour Holter ECG may be used for detecting early cardiac dysautonomia effect during anthracycline treatment with each elevated 120mg/m2 anthracycline of cumulative dose., Amaç: Kemoterapi protokollerinin temel ilacı olan antrasiklinler en sık kardiyotoksisite yan etkisine sahiptir. Antrasiklin ile tedavi edilen kanserli çocuklarda kalp hızı değişkenliğini 24 saatlik Holter elektrokardiyografi (EKG) ile prospektif olarak değerlendirmeyi amaçladık.Gereç ve Yöntemler: Antrasiklin ile tedavi edilen kanserli hastalarda hiç tedavi almadan, 120mg/m2 ve ≥240 mg/m2 kümülatif antrasiklin dozunda 24 saatlik Holter EKG monitörizasyonu yapıldı. Kalp atış hızı değişkenliğinin (HRV) zaman alanı ve frekans alanı ölçümleri elde edildi. Hastalar üç gruba ayrıldı: hiç tedavi almadan Grup 1 (n = 54), Grup 2 :≥120 mg/m2 (n = 54), Grup 3: ≥240 mg/m2 (n = 54) seklinde ayrıldı.Bulgular: Ortanca yaş 48 aydı (aralık 9-192 ay). 38 (% 70.4) hasta akut lösemi, iki hasta T lenfoblastik lenfoma (% 3.8) ve 14 hasta (% 25.8) diğer çocukluk çağı kanserleridir. Bununla birlikte, tüm kalp hızı değişkenleri, nSDNN indeksi, rMSSD, pNN50 gibi zaman parametreleri ve LF, HF ve Toplam güç gibi frekans parametreleri gibi her artan kümülatif antrasiklin dozu ile azalma görüldüğü belirlendi. LF/HF oranı da Grup 3’te istatistiksel olarak anlamlı şekilde artış gösterdiği saptandı. Kalp hızı parametrelerine göre, ortalama kalp hızı, ortalama minimum kalp hızı ve ortalama RR, kümülatif doz artıkça istatistiksel olarak anlamlı şekilde uzadığı belirlendi.Sonuç: Kalp hızı değişkenleri, kardiyak otonomik nöral disfonksiyonu ve erken miyokardiyal hasarın gösterilmesi için invazif olmayan bir tekniktir. 24 saatlik Holter EKG’si, her artan 120 mg/m2 antrasiklin kümilatif dozu ile antrasiklin tedavisi sırasında erken kardiyak dysautonomia etkisini saptamak için kullanılabilir.

Background When the COVID-19 epidemic occurred for the first time in December 2019, the governments worldwide took some restriction measures for slowing the spread of novel coronavirus. Eventually, there was a considerable decrease in volunteer blood donations. Regular transfusions and follow-up of patients with thalassemia major (TM) should be maintained during this period. It is possible that the treatment of the patients with TM may hinder due to the difficulty of reaching the treatment center and the difficulty of blood supply. Thus, in this study, we aimed to investigate whether there were any differences in the follow-up and treatment of the patients with TM during the outbreak. Materials and methods Sixty-one patients with TM who were followed up in our center without COVID-19 contact history and symptoms were included in this study. The demographic features and red blood cell volume per kilogram they received, pretransfusion hemoglobin, serum ferritin (SF) level, biochemical parameters, and transfusion interval were recorded. The difference between the arithmetic mean of the data before and during the pandemic was evaluated. Results In this study, 61 patients with TM (32 males/29 females, mean age 13.9±6.8 y) were evaluated. The mean pretransfusion hemoglobin value was 9.14±0.77 g/dL and 8.87± 0.80 g/dL before and during the pandemic, respectively (P=0.023). There was no difference between before and during the pandemic concerning transfusion interval and transfusion volume. However, SF levels increased above 1000 ng/mL in 16.6% of patients. Conclusion Although blood donation decreased significantly during the pandemic, it was observed in this study that the blood needs of patients with TM could be provided. The results of the SF level showed that the management of chelation therapy should be more meticulous. However, we should be ready for the challenges in the transfusion practice of patients with TM due to fluctuations in the COVID-19 pandemic.

The increased awareness about the severity of complications in thalassemia intermedia patients led authorities to develop strategies for better management and follow-up of these patients. In this study, we aimed to define the clinical and laboratory characteristics in previously followed-up β-thalassemia intermedia patients and wanted to gain an insight about the follow-up of this patient population in a developing country to provide them better care in the future. The mean age at diagnosis was 4 years, and the mean hemoglobin was 7.13 g/dL. The mean age at the beginning of regular transfusion was 4.8 years. An overall 74% of patients were on a regular transfusion program. The mean ferritin values at diagnosis and the last follow-up were 487 and 1225 ng/mL, respectively. The most common mutations detected in patients were IVS-I-110, IVS-I-6, IVS-II-1, and FCS 8/9 in order of frequency. Complications were seen in 48% of patients. The most common complications were osteopenia/osteoporosis (34%), growth retardation (24%), hypogonadism (18%), and cardiomyopathy (13%). In conclusion, the relatively higher complication rate in our patients who were previously treated highlights once again the need for an increased effort for optimal management and follow-up of this specific group of patients.

Congenital dyserythropoietic anemias (CDAs) are rare hereditary blood disorders characterized by ineffective erythropoiesis, hemolysis, and erythroblast morphologic abnormalities in the bone marrow. The 3 main types of CDA, I to III, and variant types of CDA, IV-VIII, have been described. The causative genes have been identified as CDAN1, C15ORF41, SEC23B, KIF23, KLF1, and GATA1. CDA type II is the most frequent form. Typical symptoms are jaundice, hepatosplenomegaly, mild-to-severe normocytic anemia, and inadequate reticulocyte response. We report an 18-year-old boy who had chronic mild congenital anemia, jaundice, and splenomegaly mimicking nonautoimmune hemolytic anemia since 18 months of age. Compound heterozygous mutations in SEC23B gene were detected by the use of a gene-targeted next-generation sequencing panel: the already reported missense mutation c.40C>T (p.Arg14Trp), and a new frameshift deletion (c.489_489delG, p.Val164Trpfs*3), confirming the diagnosis of CDA type II. The study underlines the molecular heterogeneity of CDA II and the importance of a precise diagnosis in rare congenital diseases such as CDA II. In consequence, it can be difficult to diagnose because of limited resources, financial constraint, and rarity of disease in the developing country. Advanced laboratories and new molecular approaches may help in diagnosing rare anemias.

Introduction:Inherited factor VII (FVII) deficiency is the most common of the rare bleeding disorders and shows a heterogenous distribution of bleeding phenotypes independent of factor activity level. the bleeding score (BS) evaluates the phenotype of patients with rare bleeding disorders. Thromboelastography (TEG) and thrombin generation assays (TGAs) are 2 methods to evaluate global hemostasis, and controversially both tests are useful for identifying different bleeding tendency phenotypes. the purpose of this study was to investigate the use of the BS and global assays (TEG and TGAs) to predict the bleeding phenotype of inherited FVII deficiency.Materials and Methods:A total of 27 patients with FVII deficiency were evaluated with the BS and global hemostasis assays.Results:The BS was compatible with disease severity according to the FVII activity level (P0.05). No significant correlation was observed between the factor activity level and any TEG parameter (P>0.05). the factor activity level was negatively correlated with the lag time of the TGA on the contrary positively correlated with the peak thrombin time of the TGA (P

Pyrimidine-5-nucleotidase (P5'N-1) deficiency is a rare nonspherocytic hemolytic anemia due to pyrimidine nucleotide deposition within erythrocytes. This rare erythrocyte disorder shows autosomal recessive inheritance with mutation of the pyrimidine-5'-nucleotidase gene, which is localized on 7p15-p14. Consanguinity of parents increases the probability of disease with novel mutations. Here, we report a 12-year-old boy with a delayed diagnosis of P5'N deficiency whose parents were consanguineous. He had a hemoglobin level of 7.5 g/dL, mean corpuscular volume of 93 fL, 7% reticulocyte, and lactate dehydrogenase of 678 IU/L. A peripheral blood smear showed polychromasia, marked anisopoikilocytosis with schistocytes, elliptocytes, stomatocytes, spherocytes, dacryocyte, and basophilic stippling in red blood. Decreased purine/pyrimidine ratio was 1.07 (normal range=1.4 to 2.98). Molecular analysis with direct DNA sequencing of the NT5C3 gene, codifying for P5'N-1, revealed the presence of a novel homozygous mutation, c393-394delTA, in the gene coding P5'N enzyme in the patient. To our knowledge, this is a newly defined mutation in P5'N deficiency.

Immune thrombocytopenic purpura (ITP) results from accelerated platelet destruction mediated by autoantibodies to platelet glycoproteins. Some patients with chronic ITP are refractory to all therapies [steroids, intravenous immunoglobulin (IVIG), anti-D and immunosuppresive drugs] and have chronic low platelet counts and episodic bleeding. We retrospectively evaluated the efficacy and safety of rituximab treatment and splenectomy in paediatric patients diagnosed with chronic and refractory ITP who were unresponsive to steroids, IVIG, cyclosporine and mycophenolate mofetil. Records of patients with chronic and refractory ITP in 459 patients with primary ITP who were followed up in our hospital from January 2005 to December 2014 were reviewed. Fifteen of patients received rituximab and/or applied splenectomy. Fifteen chronic ITP patients (10 boys, five girls) with a mean age of 10 years were enrolled in the study. Two of these patients were suffering from Evans syndrome. The median time since diagnosis of ITP was 10 years. The median follow-up duration after starting Rituximab and splenectomy were 13 and 9.5 months, respectively. None of the seven patients who were treated with rituximab achieved a response. A splenectomy was performed in six of the seven patients who had been treated with rituximab. Complete and partial responses were achieved in 67 and 33% of the patients, respectively. We evaluated the clinical characteristics and responses of chronic ITP patients who did not receive rituximab therapy and underwent a splenectomy. The success rate was 100% in the eight patients with chronic and refractory ITP. Rituximab therapy might not be beneficial for some children with severe chronic ITP who are refractory to standard agents. A splenectomy might be useful and preferable to rituximab. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

PubMedID: 30706992 Aim: Since the beginning of the Syrian civil war, more than 3.5 million Syrians have been under temporary protection status in Turkey. Because beta-thalassemia (BT) is a prevalent disorder in the Mediterranean countries, we decided to estimate the prevalence of and make an overview of the demographic, socioeconomic, medical characteristics, and healthcare problems of refugee children with BT. Patients: Eighteen Turkish Pediatric Hematology Oncology Centers (PHOC) with 318 refugee children from 235 families participated in the study. The mean age of the patients was 8.1 ± 4.8 years (0.5–21 years). The mean time after immigration to Turkey was 2.5 ± 1.5 years (range, 0.1–7 years). Seventy-two (22.6%) of them were born and diagnosed with BT in Turkey. On physical examination, 82 patients (26%) were underweight and 121 patients (38%) were stunted. The appearance of a thalassemic face was reported for 207 patients (65.1%). Hepatomegaly and splenomegaly were reported in 217 (68.2%) and 168 (52.8%) patients, respectively. The median ferritin level was 2508 ng/mL (range, 17–21 000 ng/mL) at the first admission, and 2841 ng/mL (range, 26–12 981 ng/mL) at the last visit after two years of follow-up in a PHOC (P > 0.05). The most frequently encountered mutation was IVSI-110 (G>A) (31%). Before immigration, only 177 patients (55.6%) reported the use of chelators; after immigration it increased to 268 (84.3%). Conclusion: Difficulties in communication, finding a competent translator capable in medical terminology, nonregular use of medications, and insensitivity to prenatal diagnosis were preliminary problems. The current extent of migration poses emerging socioeconomic and humanitarian challenges for refugee patients with BT. © 2019 Wiley Periodicals, Inc.

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.

Introduction:The most important side effect of therapeutics given for cancer treatment is febrile neutropenia. Neutropenia expected to be longer than seven days and severe neutropenia (absolute neutrophil count, Giriş: Kanser nedeniyle verilen tedavilerin en önemli yan etkilerinden febril nötropeni morbidite ve mortalitenin en önemli nedenidir. Amerika Enfeksiyon Hastalıkları Derneği tarafından mevcut nötropeninin yedi günden uzun sürmesinin beklenmesi ve derin nötropeni (mutlak nötrofil sayısı

Thymomas are the most common masses located in the anterior mediastinum, and they are often associated with autoimmune disorders including myasthenia gravis, polymyositis, and aplastic anemia (AA). Autoreactive T-cell clones generated by the thymoma may lead to autoimmune disorders. We report the case of a 14-year-old boy who was examined for AA, and the underlying cause was determined to be an immune-mediated complication of thymoma. He had no matched sibling donors. He underwent thymectomy, and 3 months later he was treated with immunosuppressive therapy (IST), consisting of antithymocyte globulin and cyclosporine A. The duration of the IST was determined to be a period of 12 months. He has recently been in complete response condition for 6 months since IST stopped. IST is a successful treatment choice for thymomas associated with AA in childhood.

Background The aim of this study was to evaluate the diagnostic utility of serum galactomannan (GM) test by investigating the impact of positivity according to different threshold levels and consecutiveness in terms of invasive aspergillosis (IA) in pediatric hematology-oncology patients. Methods Positive GM test results between January 2015 and August 2017 were reviewed, retrospectively. The children with hematological malignancies and GM positivity were included in the study and grouped according to the presence of IA. Impact of single and consecutive (3-day interval) GM positivity on IA diagnosis were evaluated according to different galactomannan index (GMI) threshold values of >0.5, >0.7, >1.0, and >1.5. Results There were 104 positive GM results from 70 patients. Forty-one patients (58.6%) had no clinical evidence of IA and categorized as the non-IA group. Invasive aspergillosis diagnosis was identified in 29 (41.4%) of the patients; 2 of them were proven and 27 were probable. Demographic characteristics and clinical findings of the patients were reviewed in Tables 1 and 2. According to different cutoff GMI values, the number of positive results was 104 for >0.5, 76 for >0.7, 57 for >1.0 and 32 for >1.5. The PPVs were low at a single GMI of >0.5 (39.4%) and reached to 50.0% with single GMI of >1.0. There was not a statistically significant difference between IA and non-IA groups in terms of different thresholds of a single GM positivity (P > 0.05) (Table 3). The number of two consecutive positive results was 34 for GMI of >0.5, 20 for GMI of >0.7, 13 for GMI of >1.0 and 4 for GMI of >1.5. In the IA group, GM positivity of consecutive results was significantly higher than non-IA group (P < 0.05). The PPVs of two consecutive positive results for GMI >0.5, GMI >0.7, GMI >1.0, and GMI >1.5 were 58.8%, 65.0%, 84.6%, and 100.0%, respectively. The effect of the GMI increase between two consecutive GM results on IA diagnosis (GM2-GM1 >0.5) was also evaluated and the PPV was found 53.8% without a statistical significance between two groups (Table 4). Conclusion When evaluated with consecutive GM positivity, the GM assay would have higher PPVs independently from the GMI cutoff value chosen. Since it may be more effective on IA diagnosis, consecutive sampling should be performed in pediatric patients at high risk. Disclosures All authors: No reported disclosures.

Chronic neutropenia (CN) is defined as neutropenia that persists for >3 months; it is caused by a heterogeneous group of diseases in children. The aim of the present study was to evaluate the significance and clinical manifestations of CN in children at a single children's hospital. Between October 2004 and April 2014, CN patient data were evaluated retrospectively. Thirty-one patients were assessed in this study. Thirteen of them (41.9%) were younger than 12 months of age at initial diagnosis. There was no difference in the absolute number of neutrophils at diagnosis between the children aged younger than 12 months and those aged 12 months and older at CN onset. Twenty-two of the patients (70.9%) were diagnosed during treatment for acute infections. A total of 11 patients (35.5%) were hospitalized because of recurrent infections. Most of the recurrent infections occurred in the lungs (81.8%). Congenital neutropenia (CoN) was identified in 14 patients (45.1%). Eight of 14 patients (57.1%) required granulocyte-colony stimulating factor treatment, and none of them experienced adverse effects from this treatment. Fifteen patients (48.3%) were diagnosed with idiopathic neutropenia. Comparison between the idiopathic and CoN groups revealed no differences in age, the absolute number of neutrophils, or the presence of infection at diagnosis; however, differences were detected in sex and the rate of spontaneous recovery from neutropenia. Ten of the patients (32.2%) experienced spontaneous recovery from neutropenia during a follow-up period of 7 to 52 months. In current study, we found a higher CoN ratio in the CN patients compared with previous reports, which may be due to the high rate of consanguineous marriages in our country. However, the finding of CN requires several laboratory investigations, prolonged follow-up, and advanced molecular analysis, and its etiology can remain idiopathic.

Primary varicella-zoster virus (VZV) infection is a benign self-limited disease. In this study, we review our experience in focusing on the outcome and treatment of VZV infection in pediatric malignancy patients. During the study period, a total of 41 patients with pediatric malignancy had been hospitalized with the diagnosis of VZV infection. All the patients were treated with intravenous acyclovir for a median of 7 days (ranging from 5 to 21 days). The calculated attributable delay of chemotherapy due to VZV infections was 8 days (ranging from 2 to 60 days). VZV-related complications were observed in 3 of 41 patients (7%) who suffered from acute respiratory distress syndrome, and one of them with hemophagocytic lymphohistiocytosis died due to respiratory failure despite acyclovir and broad-spectrum antimicrobial treatment plus supportive treatment. VZV infections are still important contagious diseases in pediatric cancer patients, because they cause not only significant mortality but also a delay in chemotherapy.Primer varisella zoster virüs (VZV) enfeksiyonu benign, kendi kendini sınırlayan bir hastalıktır. Bu çalışmada pediatrik malignitesi olan hastalarda VZV enfeksiyonu ve tedavisine odaklı tecrübelerimizi gözden geçirmeyi amaçladık. Çalışma süresi boyunca; VZV enfeksiyonu tanısı alan pediatrik maligniteli toplam 41 hasta hastaneye yatırıldı. Tüm hastalar ortalama 7 gün (5 ila 21 gün arasında değişen) intravenöz asiklovir ile tedavi edildi. VZV enfeksiyonlarına bağlı olarak hesaplanan atfedilebilir kemoterapi gecikmesi ortalama 8 gündü (2 ile 60 gün arasında değişen). VZV enfeksiyonuna bağlı komplikasyonlar 41 hastadan 3’ünde (%7) akut solunum distres sendromu olarak görüldü ve bu hastalardan hemofagositik lenfohistiyositozu olan bir tanesi asiklovir, geniş spektrumlu antibiyotik ve destekleyici tedaviye rağmen solunum yetmezliği nedeniyle kaybedildi. VZV enfeksiyonları, pediatrik malignite hastalarında hala önemli bulaşıcı hastalıklardan biridir, çünkü sadece ciddi mortaliteye sebep olmakla kalmayıp kemoterapi başlangıcını da geciktirmektedir.

Pyruvate kinase deficiency (PKD) is the most common glycolytic defect leading to hemolytic anemia. PKD is caused by the mutations in the PKLR gene; however, the detection of a decreased PK activity should be first measured for rapid diagnosis. We report here the case of a 1-year-old girl with mild hemolysis and PKD. At the time of the study, the patient showed a hemoglobin level of 9.5 g/dL, mean corpuscular volume of 93 fL, reticulocyte of 6.7%, and lactate dehydrogenase of 218 IU/L. Peripheral blood smear showed polychromasia, anisocytosis, tear drop cells, fragmented eyrtrocytes, and target cells. When a biochemical analysis was performed in our patient and her parents who had consanguinity, a decreased PK activity was detected in the patient and her father. After the molecular study of PKLR gene, a new homozygote variant, c.1708G>T (pVal570Leu), was found in our patient and her father. Her father had a misdiagnosis of Gilbert syndrome because he had unconjugated hyperbilirubinemia and not anemia. Her mother was also a carrier of the mutation in heterozygous state. Patients presenting with hemolytic anemia, either severe or mild hemolytic anemia, should be screened for PKD in the first year of life. Patients with mild hemolytic findings can be followed-up with misdiagnoses.

Background and objectives Autoimmune cytopenias are a group of heterogeneous disorders characterized by immune-mediated destruction of one or more hematopoietic lineage cells. The differential diagnosis of children with autoimmune cytopenias requires much time and laboratory investigations. The aim of the present study was to evaluate the clinical course and significance of autoimmune cytopenias due to immunodeficiency or autoimmune diseases in children at a single children`s hospital. Method Between February 1997 and September 2015, chronic/refractory autoimmune cytopenias patient data were evaluated retrospectively. Twenty-three patients were assessed in this study. Results The median duration of following was 2.6 years (4 months-18.5 years). The median age of diagnosis was 3.1 years (6 months-16 years). A total of 13 patients (56.5%) had single-lineage and 10 (46.5%) had multilineage cytopenias. The most frequent single-lineage cytopenia was thrombocytopenia, followed by anemia. In 22 of the patients, cytopenias was detected before the primary diseases. All of the patients were treated with corticosteroids or intravenous immune globulin as first-line treatment. Ten patients (43.5%) needed second or further-line immunosuppressive therapies that patients diagnosed as systemic lupus erythematosus, hypogammaglobulinemia, or common variable immunodeficiency. A total of 8 patients (34.7%) recovered from autoimmune cytopenias after the treatment of primer disease. Cytopenias were continued in 14 patients. Conclusion Cytopenia may be the first finding of an immunodeficiency or autoimmune disease and primary disease may be diagnosed in the clinical course. Taking the new targeted treatment options into consideration; early diagnosis is likely to become more important in the near-future in order to begin the treatment for the underlying disease as early as possible.

Dramatic progress in the treatment of childhood acute lymphoblastic leukemia (ALL) has been achieved during the last two decades in Western countries, where the 5-year event-free survival (EFS) rate has risen from 30 to 85 %. However, similarly high cure rates have not always been achieved in all centers in developing countries due to limited sources. We evaluated the treatment results of the ALL-Berlin-Frankfurt-Munster (BFM) 95 protocol as used between 1995 and 2009 in the pediatric hematology departments of two university hospitals. A retrospective analysis of 343 children newly diagnosed with ALL (M/F 200/143, median age 6.8 years) was performed. The overall survival (OS) and EFS according to age, initial leukocyte count, immunophenotype, chemotherapy responses (on days 8, 15, and 33), and risk groups were analyzed by Kaplan-Meier survival analysis. Median follow-up time was 6.4 years. Complete remission was achieved in 97 % of children. Five-year EFS and OS were found to be 78.4 and 79.9 %, respectively. Children younger than 6 years old had significantly better EFS and OS (83.7 and 85.2 %) than children aged a parts per thousand yen6 years (71.4 and 72.8 %). Adolescents achieved 63 % EFS and 65 % OS. Patients who had initial leukocyte counts of < 20 Au 10(9)/L had better EFS and OS (82.2 and 84.6 %) than children with higher initial leukocyte counts (72.6 and 72.6 %). EFS for B-cell precursor and T-cell ALL was 81.5 and 66.7 %, respectively. Children with a good response to prednisolone on day 8 (87 %) achieved significantly better EFS and OS (81.2 and 81.9 % vs. 55.3 and 60.5 %). Children whose bone marrow on day 15 was in complete remission had higher EFS and OS (83.7 and 86.6.1 % vs. 56.4 and 61.5 %). Children in the standard-risk and medium-risk groups obtained statistically significantly higher EFS (95.5 and 82.7 %) and OS (97.7 and 82.3 %) compared to the high-risk group (EFS 56.3 %, OS 63.4 %). The relapse rate was 14.8 %. The median relapse time from diagnosis was 23.2 months. Death occurred in 69 of 343 patients (20.1 %). The major causes of death were infection and relapse. None of the patients died of drug-related toxicity. The ALL-BFM 95 protocol was applied successfully in these two centers. In developing countries in which minimal residual disease cannot be monitored, this protocol can still be used with high survival rates.

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.

WOS: 000401520200012, PubMed ID: 28169428, The genetic basis of haemophagocytic lymphohistiocytosis (HLH) has not been elucidated in 10% of affected patients. In this study, we report four HLH episodes in three patients with HAX1 gene mutations. We screened the mutations associated with congenital neutropenia (CN) because the neutropenia persisted following HLH treatment. There were homozygous HAX1 mutations detected in all patients. This is the first case series of patients with CN caused by HAX1 mutation who presented with HLH. We hypothesize that severe neutropenia persists after an HLH episode in children without HLH mutations (especially infants) because these patients have CN caused by HAX1 mutations.

Munchausen syndrome by proxy (MBP) is an extreme form of child abuse where children were unnecessarily treated or investigated for medical conditions that were falsified by their caregivers. Here the authors report a 16-year-old female with the complaints of bleeding from multiple and unusual sites, including hemoptysis, hematuria, bloody tears, and bloody nipple discharge, all of which are only witnessed by her mother. Extensive investigation revealed no organic etiologies for bleeding. The diagnosis of MBP was put by a multidisciplinary team. The diagnosis of MBP must be kept in mind in conditions where there is no underlying organic pathology in a bleeding patient.

Methotrexate (MTX) is an essential component of chemotherapy for childhood acute lymphoblastic leukemia (ALL). Both intravenous and most commonly intrathecal routes of MTX have been implicated in acute, subacute, and chronic neurotoxicity syndromes. Subacute MTX neurotoxicity occurs within days to weeks after the intravenous or intrathecal therapy and characterized by a distinct presentation with remarkable clinical resemblance to stroke, including hemiparesis, hemisensory deficits, aphasia, dysarthria, dysphagia, and diplopia. Herein the authors describe the clinical and typical neuroimaging features of a female patient with ALL who presented with subacute MTX neurotoxicity that rapidly progressed to a severe clinical condition in a few hours but eventually resolved completely with dexamethasone and folinic acid. Subacute MTX neurotoxicity is a transient neurological dysfunction that should be considered in patients presenting with stroke-like and various neurological symptoms 10 to 14 days after intrathecal therapy and diffusion-weighted magnetic resonance imaging should be undertaken for the correct diagnosis and exclusion of possible ischemic infarct. Discontinuation of subsequent intrathecal MTX therapies should be considered in severe cases and treatment with dexamethasone and folinic acid may help to resolve the symptoms.

Central nervous system bleeding, which can be a life-threatening complication, is seen in 2.7% of patients with haemophilia. Spinal epidural haematomas represent about one-tenth of such cases. Here, we report on a 10-month-old boy with severe haemophilia A, who presented with torticollis. Although administration of factor VIII at a dose of 50 U/kg, the patient developed flaccid paralysis of the upper extremities. Factor VIII inhibitor screen was positive. Magnetic resonance imaging of the spine revealed spinal epidural haematomas, extending from C-1 to the cauda equina. Treatment was continued with recombinant activated factor VIIa without surgery. After 1 month, complete neurological recovery was achieved and fully resolved haematomas were detected on spinal MRI. A prompt radiological evaluation of the cervical spine with MRI should be made in patients with haemophilia presenting with torticollis. In addition, in the case of life-threatening bleeding in patients with haemophilia, the possibility of an inhibitor should be kept in mind.

The granulocyte transfusion (GTX) has been used for a long time due to uncontrolled neutropenic fever with antimicrobial agents. In some cases, the product needs to be splitted for using in the next 12 hours. The aim of this study is to evaluate the efficacy of splitted product and clinical response to GTX. In this study, 15 patients with malignancy with 19 neutropenic fever, who had received 56 GTX, were included. Seventeen of 56 GTX were splitted and used in maximum 12 hours during infections which did not respond to antibacterial and antifungal therapy in 7 days. The patients were divided in to response groups as a complete, partial and progressive. The predictive factors for response group were evaluated. GTX were well tolerated in all patients. The median granulocyte dose was 1.26 (0.38-5.22) × 10(9)/kg. Total response rate was 89.5%. The infection-related mortality rate was 10.5%. Although the granulocyte doses are the same in both of the product groups, an hour later ANC increment of primer product was higher than that of splitted product (p = 0.001). Among the products, 48.7% of primer product and 17.6% of splitted product had induced ≥ 1000/mm(3) ANC increment after an hour (p = 0.039). Granulocyte transfusion is safe and effective in controlling the febrile neutropenia attack. GTX should be applied in a short time to provide effective ANC increment. For now, main granulocyte product instead of splitted product should be preferred in case of uncontrolled neutropenic fever with antibacterial/antifungal agents.

WOS: 000219056100012, The association between 6-Thioguanine (6-TG) treatment and drug-induced liver injury has been reported since 1976. Recent reports have suggested that treatment of patients with 6-TG can lead to chronic hepatotoxicity and portal hypertension. Most of the cases reported to have 6-TG related hepatotoxicity had acute lymphoblastic leukemia or inflammatory bowel disease. In this case report, we discussed the diagnosis and approach in an acute myeloid leukemia patient who developed 6-TG related chronic hepatotoxicity.

Idiopathic pulmonary hemosiderosis (IPH) is an uncommon chronic disorder in children. It is characterized by recurrent pulmonary hemorrhage and may result in hemoptysis and pulmonary insufficiency. The most common hematologic manifestation of IPH is iron deficiency anemia. The etiology of IPH is not known and its diagnosis may be difficult due to the variable clinical courses. The most helpful signs for identifying IPH are iron deficiency anemia and recurrent or chronic cough, hemoptysis, dyspnea, wheezing. We report here 5 pediatric cases of IPH presenting with iron deficiency anemia and without pulmonary symptoms. Mean corpuscular volume was low in all patients; iron was low in 4 out of 5 cases; total iron binding capacity was high in all of them; ferritin was low in 3 patients. At follow up, none of them had responded successfully to the iron therapy. Although they didn’t present with pulmonary symptoms, chest radiographs incidentally revealed diffuse reticulonoduler shadows in all of them. Computed tomography revealed diffuse ground-glass opacities, consolidation, increased density. The diagnosis was confirmed by the detection of hemosiderinladen macrophages in bronchoalveolar lavage fluid and gastric aspirate. If patients with iron deficiency anemia don’t respond to iron therapy, they should be examined for IPH. Chest radiographs should be taken even in absence of pulmonary symptoms. Early diagnosis is important for a timely management of IPH.