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Background/Aim: Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood. Patients usually present with fatigue, pallor, weight loss, and joint and/or bone findings. However, the effects of bone-associated symptoms on prognosis remains controversial. We aimed to demonstrate whether bone-associated symptoms affect prognosis in children with ALL. Methods: This retrospective cohort study included the data from 268 patients with ALL who were diagnosed and treated between January 2011 and December 2020. The patients were divided into two groups as those with and without bone-associated symptoms. We compared the groups in terms of age, gender, immunophenotyping, day 8 prednisolone response, and risk groups, in addition to minimal residual disease (MRD), relapse, and survival rates. Results: Eighty-five out of 268 (32%) children had bone-associated symptoms at the time of diagnosis, whereas others (n=183) had none of these symptoms. The relapse rate in children with bone-associated symptoms was found to be higher than the others (17.6% versus 12%), but the difference was not significant (P=0.24). However, children with bone findings developed earlier relapse when compared with the others (18.6 versus 28.6 months; P

The clinical presentation of chronic myeloid leukemia (CML) at diagnosis differs in children compared to adults. At younger age, anemia appears to be frequent at diagnosis, but its prevalence and its impact on prognosis are not well known. In the International Registry of Childhood CML, we selected children and adolescents in chronic phase at diagnosis of CML and treated upfront with imatinib. We examined their hemoglobin level at diagnosis according to the WHO grades to assess the prevalence of anemia and its impact on response to tyrosine kinase inhibitors (TKIs). Data on 430 patients were included. Anemia at diagnosis was observed in 350 patients (81%), with a mean hemoglobin level of 96.4 g/l (SD 23.6). Among them, 182 patients (52%) presented with moderate anemia and 110 (31%) with severe anemia while 58 (17%) had mild anemia. Compared with mild and no anemia, moderate and severe forms were significantly associated with younger age at diagnosis, asthenia, splenomegaly, and increased leukocyte and basophil counts. Delays in achieving major and deep molecular responses were significantly increased for patients with moderate and severe anemia, and also failure of imatinib treatment was more frequent in these two sub-cohorts. However, hemoglobin level was not significantly associated with survival. Anemia at diagnosis of pediatric CML was frequent and may be considered as a prognostic factor.

Central venous catheters (CVCs) are important for maintenance of childhood leukemia treatment but CVCs may develop complications. The aim of this study was to retrospectively evaluate the CVC-related complication rate, complication types, and outcome in children with acute leukemia. Complications developing in 310 CVCs (ports n=250, Hickman catheters n=60) inserted in 262 patients were evaluated. A total of 225,296 catheter days were screened. Median (range) CVC in-dwelling time was 661.5 (1 to 2636) days. In total, 157 complications developed of which 91 (58%) were infectious complications, 35 (22.3%) were vascular, 19 (12.1%) were surgical, and 12 (7.6%) were mechanical. Hickman catheters had a higher complication rate and were more prone to mechanical complications ( P0.01) but there was no difference for other complications. A lower absolute neutrophil count at insertion was observed in children with infectious complications ( P0.01). Seventy-eight of 136 catheters (57.3%) had to be removed prematurely. The overall complication rate was 0.65 per 1000 catheter days. In multivariate analysis, relapse leukemia, Hickman catheter and low absolute neutrophil count increased complication risk by 4.00, 1.97, and 1.92 times, respectively. Five (1.9%) deaths occurred because of catheter complications. Safe use of CVCs can be improved by early detection of complications and an experienced catheter care team.

Background Refugee or asylum seekers (RAS) children are at increased risk of physical, developmental, and behavioral health issues. The aim of this study was to evaluate clinical and psychosocial outcomes of hematopoietic stem cell transplantation (HSCT) in RAS children and compare health-related quality of life (HRQOL) to those of Turkish peers. Methods This retrospective study included patients who underwent HSCT aged 0-18 years and completed 100-day post-transplant. The PedsQL 4.0 Generic Core Scale was used in children over 5 years old to compare HRQOL. Results A total of 166 RAS patients (M/F: 106 /60) underwent 174 HSCTs (six patients had two, and one had three HSCT) compared to 66 Turkish patients. The mean age of the patients in the RAS group was 7.8 +/- 4.9 years and similar to controls. A total of 124 patients (75%) were from Syria, and 49 (25%) were from other countries in the Middle East and Africa. The cause of migration was war in 121 (74%) RAS patients. Complications of HSCT were no different between the groups. However, the rate of neutropenic sepsis was significantly higher in the RAS group (p = 0.004). The total scores of HRQOL were not different between RAS and controls. In the RAS group, ratings of social functioning were lower in patients with consanguinity or non-malignant disease or who had match-related donors. Discussion Identifying areas of difficulty in subscales of HRQOL may help physicians to classify patients who need additional supportive care. Regular monitoring and supporting physical needs may result in better functional outcomes after HSCT.

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

Objective Hemophilia A (HA) is the most severe X-linked inherited bleeding disorder caused by hemizygous mutations in the factor 8 (F8) gene. The aim of this study is to determine the mutation spectrum of the F8 gene in a large HA cohort from Turkey, and then to establish a phenotype-genotype correlation. Materials and methods All HA cases (270 patients) analyzed molecularly in the Ege University Pediatric Genetics Molecular Laboratory between March 2017 and March 2018 were included in this study. To identify intron 22 inversion (Inv22), intron 1 inversion (Inv1), small deletion/insertions, and point mutations, molecular analyses of F8 were performed using a sequential application of molecular techniques. Results The mutation detection success rate was 95.2%. Positive Inv22 was found in 106 patients (39.3%), Inv1 was found in 4 patients (1.5%), and 106 different disease-causing sequence variants were identified in 137 patients (50.6%). In 10 patients (3.7%), amplification failures involving one or more exonic regions, considered to be large intragenic deletions, were identified. Of 106 different F8 mutations, 36 were novel. The relationship between F8 genotype and inhibitor development was considered significant. Conclusion A high mutation detection rate was achieved via the broad molecular techniques applied in this study, including 36 novel mutations. With regard to mutation types, mutation distribution and their impact on clinical severity and inhibitor development were found to be similar to those previously reported in other hemophilia population studies.

Micafungin is recommended especially in patients with liver and kidney failure and in the presence of other side effects due to antifungals apart from its known priority indications such as invasive candidiasis. The aim of this study was to evaluate the children who have received micafungin treatment. In the study, 125 children who were hospitalized in the pediatric wards and intensive care units of our hospital and had used micafungin between November 2016 and January 2019 were analyzed retrospectively. Clinical data, micafungin indication, blood values on the first and fourth days of the treatment, side effects of the drug and efficacy were evaluated. Sixty percent (75/125) of the patients were male and the mean age of all the patients were 58 ± 67 (0-215, 30) months. Approximately half of the cases (48%) had malignancy and 13% of them were premature. Sixty-two percent (n= 37) of the malignencies were hematological (27 acute lymphocytic leukemia, nine acute myeloid leukemia, one myelodysplastic syndrome) and 38% (n= 23) were oncological (six neuroblastoma, four Hodgkin lymphoma, two Non-Hodgkin's lymphoma, five sarcomas, one hepatoblastoma, five others) malignencies. The major cause of hospitalization was sepsis (53%). The patients had several risk factors like immunosuppressive therapy (n= 68, 54%), neutropenia (n= 61, 49%), central venous catheter (n= 102, 82%), nasogastric tube (n= 63, 50%), endotracheal intubation tube (n= 49, 39%), urinary catheter (n= 14, 11%) and total parenteral nutrition (n= 81, 65%). Thirteen percent (n= 16) of the cases were post-operative patients. Candida species were cultivated in 97 clinical specimens (blood, endotracheal aspirate, sputum, urine, etc.) among 23 (18%) of the patients. Thirteen (10%) of the patients had candidemia and 62% of them were non-albicans strains. In all candidemias, strains were echinocandin susceptible, and blood cultures were negative within four days. When all the patients (n= 125) were evaluated, a significant decrease in C-reactive protein, an increase in sodium, and a decrease in alanine aminotransferase were observed on the fourth day of micafungin treatment (p

The incidence of invasive fungal infections (IFIs) has increased due to intensive chemotherapy in childhood leukemia. The aim of this study was to evaluate the incidence, risk factors, causative pathogens, and impact on survival of IFIs among pediatric leukemia patients.The hospital records of 307 children with acute lymphoblastic leukemia (ALL, n=238), acute myeloid leukemia (AML, n=51), and relapsed leukemia (n=18) between January 2010 and December 2015 were retrospectively evaluated.A total of 1213 febrile neutropenia episodes were recorded and 127 (10.4%) of them were related to an IFI. Of 307 children, 121 (39.4%) developed IFIs. The mean age was significantly older in the IFI group compared to children without IFIs (p0.001). IFIs were defined as possible, probable, and proven in 73.2%, 11.9%, and 14.9% of the attacks, respectively. Invasive aspergillosis (81.9%) was the most frequent infection, followed by invasive candidiasis (13.4%) and rare fungal diseases (4.8%). The majority of IFI attacks in both ALL and AML occurred during the induction phase. In total, the death rate was 24% and the IFI-related mortality rate was 18%. The mortality rate among children with IFIs was found to be significantly higher than that of children without IFIs (p0.001). Overall and event-free survival rates at 5 years were also found to be significantly lower in the IFI group (p0.001). Relapse (odds ratio: 8.49) was the most effective risk factor for mortality, followed by developing an IFI episode (odds ratio: 3.2) and AML (odds ratio: 2.33) according to multivariate regression analysis.Our data showed that IFIs were more common in older children. Although proven and probable IFI episodes were more frequently diagnosed in cases of relapse and AML, children with ALL and AML had similar frequencies of experiencing at least one episode Conclusion: Our data showed that IFIs were more common in older children. Although proven and probable IFI episodes were more frequently diagnosed in cases of relapse and AML, children with ALL and AML had similar frequencies of experiencing at least one episodeÇocukluk çağı lösemisinde yoğun kemoterapi nedeniyle invaziv mantar enfeksiyonlarının (IFI) insidansı artmıştır. Bu çalışmanın amacı, pediatrik lösemi hastalarında IFI’nın insidansını, risk faktörlerini, nedensel patojenleri ve sağkalım üzerindeki etkisini değerlendirmektir.Ocak 2010 ile Aralık 2015 tarihleri arasında akut lenfoblastik lösemili (ALL, n=238), akut myeloid lösemili (AML, n=51) ve relaps lösemili (n=18) 307 çocukların hastane kayıtları geriye dönük olarak değerlendirildi.Toplam 1213 febril nötropeni atağı kaydedildi ve bunların 127’si (%10,4) IFI ile ilgiliydi. Bu 307 çocuğun 121’i (%39,4) IFI geliştirdi. Ortalama yaş, IFI grubunda IFI olmayan çocuklara kıyasla anlamlı olarak daha büyük bulundu (p0,001). IFI, atakları sırasıyla; %73,2, %11,9 ve %14,9’unda olası, yüksek olası ve kanıtlanmış olarak tanımlandı. İnvazif aspergilloz (%81,9) en sık görülen enfeksiyondu, bunu invaziv kandidiyazis (%13,4) ve nadir mantar hastalıkları (%4,8) izledi. Hem ALL hem de AML’deki IFI ataklarının çoğu indüksiyon aşamasında görüldü. Toplamda ölüm oranı %24 ve IFI bağlantılı ölüm oranı %18 olarak bulundu. IFI’lı çocuklarda ölüm oranı, IFI olmayan çocuklarda anlamlı olarak daha yüksek bulundu (p0,001). Beş yılda genel ve olaysız sağkalım, IFI grubunda önemli ölçüde daha düşük bulundu (p0,001). Relaps (odds oranı, 8,49), mortalite üzerinde en etkili risk faktörü oldu ve bunu, çok değişkenli regresyon analizi ile bir IFI epizodu geçirmek (odds oranı, 3,2) ve AML olmak (odds oranı, 2,33) izledi.Çalışmamız, IFI’nın büyük yaştaki çocuklarda daha yaygın olduğunu gösterdi. Kanıtlanmış ve olası IFI epizodlarının nüks ve AML’de daha sık saptanmasına karşın, ALL ve AML’li çocukların da benzer sıklıkta en az bir IFI atağı geçirdiği görüldü. Nadir mantar hastalıkları önemli bir sorun olarak tanımlandı. Tedavideki başarıya rağmen, IFI’nın akut lösemili çocuklarda ölüm oranını artırdığı saptandı.

We report the national data on the outcomes of hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) patients in Turkey on behalf of the Turkish Pediatric Stem Cell Transplantation Group. We retrospectively enrolled 1469 patients with TM who underwent their first HSCT between 1988 and 2020 in 25 pediatric centers in Turkey. The median follow-up duration and transplant ages were 62 months and 7 years, respectively; 113 patients had chronic graft versus host disease (cGVHD) and the cGVHD rate was 8.3% in surviving patients. Upon the last visit, 30 patients still had cGvHD (2.2%). The 5-year overall survival (OS), thalassemia-free survival (TFS) and thalassemia-GVHD-free survival (TGFS) rates were 92.3%, 82.1%, and 80.8%, respectively. cGVHD incidence was significantly lower in the mixed chimerism (MC) group compared to the complete chimerism (CC) group (p < 0.001). In survival analysis, OS, TFS, and TGFS rates were significantly higher for transplants after 2010. TFS and TGFS rates were better for patients under 7 years and at centers that had performed over 100 thalassemia transplants. Transplants from matched unrelated donors had significantly higher TFS rates. We recommend HSCT before 7 years old in thalassemia patients who have a matched donor for improved outcomes., Turkish Society of Pediatric Hematology, We would like to thank Vedat Uygun for contributing to the statistics of the study. This study was supported by the Turkish Society of Pediatric Hematology.

This study aimed to evaluate systemic thrombolysis experiences with recombinant tissue plasminogen activator (rtPA).Retrospective data were collected from 13 Turkish pediatric hematology centers. The dose and duration of rtPA treatment, concomitant anticoagulant treatment, complete clot resolution (CCR), partial clot resolution (PCR), and bleeding complications were evaluated. Low-dose (LD) rtPA treatment was defined as 0.01-0.06 mg/kg/h and high-dose (HD) rtPA as 0.1-0.5 mg/kg/h.Between 2005 and 2019, 55 thrombotic episodes of 54 pediatric patients with a median age of 5 years (range: 1 day to 17.75 years) were evaluated. These patients had intracardiac thrombosis (n=16), deep vein thrombosis (DVT) (n=15), non-stroke arterial thrombosis (n=14), pulmonary thromboembolism (PE) (n=6), and stroke (n=4). The duration from thrombus detection to rtPA initiation was a median of 12 h (range: 2-504 h) and it was significantly longer in cases of DVT and PE compared to stroke, non-stroke arterial thrombosis, and intracardiac thrombosis (p=0.024). In 63.6% of the episodes, heparin was initiated before rtPA treatment. LD and HD rtPA were administered in 22 and 33 of the episodes, respectively. Concomitant anticoagulation was used in 90% and 36% of the episodes with LD and HD rtPA, respectively (p=0.0001). Median total duration of LD and HD rtPA infusions was 30 h (range: 2-120 h) and 18 h (2-120 h), respectively (p=0.044). Non-fatal major and minor bleeding rates were 12.5% and 16.7% for LD and 3.2% and 25.8% for HD rtPA, respectively. At the end of the rtPA infusions, CCR and PCR were achieved in 32.7% and 49.0% of the episodes, respectively. The most successful site for thrombolysis was intracardiac thrombosis. HD versus LD rtPA administration was not correlated with CCR/PCR or bleeding (p0.05).Systemic thrombolytic therapy may save lives and organs effectively if it is used at the right indications and the right times in children with high-risk thrombosis by experienced hematologists with close monitoring of recanalization and bleeding.Geriye dönük çok merkezli bir çalışma düzenleyerek, çocuk hematoloji uzmanlarının sistemik rekombinant doku plazminojen aktivatörü (rtPA) kullanımı ile ilgili deneyimlerinin ortaya konması amaçlandı.Türkiye’deki 13 pediatrik hematoloji merkezinden geriye dönük veriler toplandı. rtPA tedavisinin dozu ve süresi, eşzamanlı antikoagülan tedavi, tam pıhtı erimesi (TPE), kısmi pıhtı erimesi (KPE) ve kanama komplikasyonları değerlendirildi. Düşük doz (DD) rtPA tedavisi 0,01-0,06 mg/kg/saat ve yüksek doz (YD) 0,1-0,5 mg/kg/saat olarak tanımlandı.2005-2019 yılları arasında ortanca yaşı 5 yıl (1 gün-17,75 yıl) olan 54 hastanın 55 trombotik epizodu değerlendirildi. Hastaların tanıları; intrakardiyak tromboz (n=16), derin ven trombozu (DVT) (n=15), inme dışı arteriyel tromboz (n=14), pulmoner tromboemboli (PE) (n=6) ve inme (n=4) idi. Trombüs saptanmasından rtPA başlangıcına kadar geçen süre medyan 12 saat (2 sa-504 sa) idi ve inme, inme olmayan arteriyel tromboz ve intrakardiyak tromboza kıyasla DVT ve PE için anlamlı olarak daha uzundu (p=0,024). Atakların %63,6’sında rtPA tedavisinden önce heparin başlandı. Atakların 22’sine DD ve 33’üne YD rtPA uygulandı. DD ve YD rtPA ataklarının sırasıyla %90’ında ve %36’sında eş zamanlı antikoagülasyon kullanıldı (p=0,0001). DD ve YD rtPA infüzyonlarının medyan toplam süresi sırasıyla 30 sa (2 sa-120 sa) ve 18 sa (2 sa-120 sa) idi (p=0,044). Ölümcül olmayan majör ve minör kanama oranları DD için sırasıyla %12,5, %16,7 ve YD rtPA için %3,2, %25,8 idi. rtPA infüzyonlarının sonunda, atakların sırasıyla %32,7’sinde TPE ve %49’unda KPE elde edildi. Tromboliz için en başarılı bölge intrakardiyak trombozdu. YD’ye karşı DD rtPA uygulaması, TPE/KPE veya kanama ile korele değildi (p0,05).Yüksek riskli trombozlu çocuklarda sistemik trombolitik tedavi, deneyimli hematologlar tarafından rekanalizasyon ve kanamanın yakın takibi altında doğru endikasyon ve doğru zamanda kullanıldığında etkin bir şekilde hayat ve organ kurtarabilir.

Giriş: Lösemi, multifaktöriyel bir hastalıktır. Bazı genetik sendromların lösemi sıklığını artırdığı iyi bilinmektedir. Biz çalışmamızda sendromik olmayan malformasyon ile lösemi ilişkisini değerlendirdik. Gereç ve Yöntem: Akut lösemi tanısı almış 288 hasta çalışmaya dahil edildi. Malign olmayan hematolojik hastalığı olan 201 hasta kontrol grubu olarak kabul edildi. Sendromik çocuklar her iki grupta da dışlandı. Tüm çocuklar ICD-10, Bölüm XVII’ye göre konjenital malformasyon açısından muayene edildi. Her iki grupta malformasyonların tipi ve sayısı karşılaştırıldı. Bulgular: Tanı anındaki yaş, cinsiyet, ebeveynler arasında akrabalık, anne babanın doğum yaşı, ailede kanser öyküsü ve annenin önceki gebelikleri açısından lösemi ve kontrol grubu arasında fark yoktu. Lösemili popülasyonda konjenital malformasyonlar daha fazla görüldü (p

We investigated the health-related quality of life (HRQL) in survivors of pediatric acute lymphoblastic leukemia (ALL) and evaluated the perceptions of the children, their siblings, and their parents.Seventy ALL survivors, who were between 7 and 17 years of age and had completed therapy ≥2 years, were included. The control group consisted of their healthy siblings. HRQL was assessed by the age-specific KINDLNo significant differences could be found among HRQL scores of ALL survivors with respect to variables such as sex, risk group, and having chronic illness. HRQL scores for physical well-being, emotional well-being, family, and social functioning of the patient and sibling self-reports and parent proxy reports were lower than the expected values for healthy and chronically ill children.These results demonstrate that both ALL survivors and their families need help via psychological counseling programs to improve their HRQL even after completion of therapy.Çocukluk çağı akut lenfoblastik lösemi (ALL) sağ kalanlarında sağlıkla ilişkili yaşam kalitesinin (HRQL) araştırılması ve çocukların, kardeşlerinin ve ebeveynlerinin bununla ilgili algılamalarının değerlendirilmesi amaçlandı.Çalışma grubu 7-17 yaş arası, kemoterapisi en az 2 yıl önce tamamlanmış 70 ALL’li çocuktan oluşturuldu. Kontrol grubu hastaların sağlıklı kardeşlerini (n=32) içerdi. HRQL ölçümü için yaşa uygun KINDLALL sağ kalanlarında HRQL skorları cinsiyet, risk grubu, kronik hastalığı olma ve relaps öyküsü açısından istatistiksel anlamlı fark göstermedi. Hastalar ve kardeşlerinin HRQL skorlarıyla ebeveynlerin hasta çocuklarının durumuna bakış açısı skorları değerlendirildiğinde fiziksel iyilik, duygusal iyilik, aile ve sosyal ilişkiler ile ilgili HRQL skorları sağlıklı ve kronik hastalığa sahip çocuklara göre düşük bulundu.Hasta ve ebeveynlerin HRQL skorlarının düşük saptanması çocukluk çağı ALL sağ kalanları ve ebeveynlerinin tedavi bitimi sonrasında da psikolojik danışmanlık programlarına ihtiyacı olduğunu göstermektedir.

Objectives: This study aims to investigate, retrospectively, the epidemiological and clinical characteristics, laboratory results, radiologic findings and outcomes of novel coronavirus disease-19 (COVID-19) in patients with transfusion dependent β thalassemia (β-thalassemia major-TM), non-transfusion dependent β thalassemia (β-thalassemia intermedia -TI) and sickle cell disease (SCD). Design, setting: A total of 17 Centers, from 10 countries, following 9,499 patients with hemoglobinopathies participated in the survey. Main outcome measures: Clinical, laboratory and radiologic findings and outcomes of patients with COVID-19 were collected from medical records and summarized. Results: A total of 13 patients, 7 with TM, 3 with TI and 3 with SCD, with confirmed COVID-19, were identified from 6 Centers from different countries. The overall mean age of patients was 33.7±12.3 years (range:13-66); 9/13 (69.2%) patients were females. The commonest symptoms in the 10 symptomatic patients were: fever (80%), cough (70%), headache (60%), fatigue (60%), gastrointestinal symptoms (diarrhea /vomiting/abdominal pain; 50%), tachypnea/dyspnea (40%), and sore throat (40%). Six patients had pneumonia (unilateral, bilateral or multiple opacity) and 4 needed oxygen therapy. An oxygen saturation ≤ 93% was documented in 3 patients at diagnosis. 6/10 patients had an exacerbation of anemia (2 with SCD, associated with back and chest pain in 1 patient), and 3 (

Micafungin is recommended especially in patients with liver and kidney failure and in the presence of other side effects due to antifungals apart from its known priority indications such as invasive candidiasis. The aim of this study was to evaluate the children who have received micafungin treatment. In the study, 125 children who were hospitalized in the pediatric wards and intensive care units of our hospital and had used micafungin between November 2016 and January 2019 were analyzed retrospectively. Clinical data, micafungin indication, blood values on the first and fourth days of the treatment, side effects of the drug and efficacy were evaluated. Sixty percent (75/125) of the patients were male and the mean age of all the patients were 58 ± 67 (0-215, 30) months. Approximately half of the cases (48%) had malignancy and 13% of them were premature. Sixty-two percent (n= 37) of the malignencies were hematological (27 acute lymphocytic leukemia, nine acute myeloid leukemia, one myelodysplastic syndrome) and 38% (n= 23) were oncological (six neuroblastoma, four Hodgkin lymphoma, two Non-Hodgkin's lymphoma, five sarcomas, one hepatoblastoma, five others) malignencies. The major cause of hospitalization was sepsis (53%). The patients had several risk factors like immunosuppressive therapy (n= 68, 54%), neutropenia (n= 61, 49%), central venous catheter (n= 102, 82%), nasogastric tube (n= 63, 50%), endotracheal intubation tube (n= 49, 39%), urinary catheter (n= 14, 11%) and total parenteral nutrition (n= 81, 65%). Thirteen percent (n= 16) of the cases were post-operative patients. Candida species were cultivated in 97 clinical specimens (blood, endotracheal aspirate, sputum, urine, etc.) among 23 (18%) of the patients. Thirteen (10%) of the patients had candidemia and 62% of them were non-albicans strains. In all candidemias, strains were echinocandin susceptible, and blood cultures were negative within four days. When all the patients (n= 125) were evaluated, a significant decrease in C-reactive protein, an increase in sodium, and a decrease in alanine aminotransferase were observed on the fourth day of micafungin treatment (p0.05). A total of 39 (31%) patients underwent various antifungal treatments for median seven (1-60) days prior to micafungin treatment. Fourteen (36%) of these 39 patients, had elevated liver function tests (LFT), 10 (26%) of them had hypokalemia, and five (13%) of them had elevated renal function tests. Ten (26%) patients had antifungal-induced hypokalemia previously; and potassium levels were normalized after micafungin treatment (p= 0.0001). The patients for which micafungin treatment was chosen due to elevated liver function tests (n= 47, 38%), whether the antifungalinduced or not; alanine aminotransferase and aspartate aminotransferase levels were decreased after micafungin treatment (p= 0.0001 and p= 0.0001, respectively). Nineteen (15%) of the patients have died within the first 30 days of micafungin treatment and one of them had candidemia. No micafungin treatment related significant side effects were observed in any of the patients. Our study showed that micafungin could be a safe and effective option in pediatric cases including newborns with high liver and kidney function tests.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare inflammatory syndrome resulting from uncontrolled proliferation in the monocyte / macrophage system. It is divided into two classes as familial (primary) and secondary. Since the rate of consanguineous marriage in our country is high with 29.2%, the frequency of HLH is also increasing. Secondary HLH can be seen at any age, but its true incidence is unknown. It can accompany malignancies, infections and inflammatory processes. Major clinical findings are persistent high fever, cytopenia, splenomegaly and / or hepatomegaly. The first finding is usually fever. The goal of treatment is to stop abnormal inflammation and treat the underlying cause.MATERIALS and METHODS: We retrospectively reviewed 15 patients diagnosed and treated in our clinic between 2010 and 2019. Statistical analysis was performed with kruskal-wallis test.RESULTS: The median age of diagnosis of 15 patients diagnosed and treated in our clinic was 18 months (1 month-17 years). The female to male ratio was 6/9. Fever was seen in all patients, hepatosplenomegaly was 80%. The mean ferritin value was 33.927 ± 51.461µ / l (964-201.074). In our patient group, consanguineous marriage rate was 53% (n = 8) and it was high and the factor was EBV in all patients who developed secondary to infection. 33% (n = 5) of the cases were primary and 67% (n = 10) were secondary. 40% (n = 4) of secondary cases had malignancy in etiology, 50% (n = 5) infection and 10% (n = 1) metabolic disease.CONCLUSIONS: HLH is important for early diagnosis in cases with persistent high fever, hepatosplenomegaly and high ferritin conditions in our country. In cases presenting with HLH, malignancy should not be forgotten in etiology besides primary causes., GİRİŞ ve AMAÇ: Hemofagositik lenfohistiyositoz (HLH) monosit/makrofaj sistemindeki kontrolsüz proliferasyon sonucu oluşan nadir görülen enflamatuar bir sendromdur. Ailesel (primer) ve sekonder olmak üzere iki sınıfa ayrılmaktadır. Ülkemizde akraba evliliği oranı %29.2 ile yüksek olduğu için HLH sıklığı da artmaktadır. Sekonder HLH her yaşta görülebilmekle beraber gerçek insidansı bilinmemektedir. Maligniteler, enfeksiyonlar ve inflamatuar süreçlere eşlik edebilir. Major klinik bulgular persistan yüksek ateş, sitopeni, splenomegali ve/veya hepatomegalidir. İlk bulgu genellikle ateştir. Tedavide amaç anormal inflamasyonu durdurmaktır ve altta yatan nedeni tedavi etmektir.YÖNTEM ve GEREÇLER: Kliniğimizde 2010 ile 2019 yılları arasında tanı konulup tedavi edilen 15 hastayı retrospektif olarak değerlendirdik. İstatistiksel analiz kruskal- wallis testi ile yapıldı.BULGULAR: Kliniğimizde tanı alıp tedavi edilen 15 hastanın ortanca tanı yaşı 18 aydı(1ay- 17 yaş). Olguların kız erkek oranı 6/9 idi. Ateş bütün hastalarda görüldü, hepatosplenomegali %80 oranında vardı. Ortalama ferritin değeri 33.927±51.461µ/l (964-201.074)idi. Hasta grubumuzda akraba evliliği oranı %53 (n=8) olup yüksekti ve enfeksiyona sekonder gelişen hastaların tümünde etken EBV idi. Olguların %33’ü (n=5) primer, %67’si(n=10) sekonderdi. Sekonder olguların %40’ında(n=4) etyolojide malignite, %50’sinde (n=5) enfeksiyon ve %10’unda (n=1) metabolik hastalık vardı.TARTIŞMA ve SONUÇ: Ülkemiz koşullarında persistan yüksek ateş,hepatosplenomegali ve ferritin yüksekliği ile gelen olgularda HLH düşünülmesi erken tanı açısından önemlidir. HLH tablosu ile gelen olgularda primer nedenler yanı sıra etyolojide malignite de unutulmamalıdır

INTRODUCTION Chronic myeloid leukemia (CML) is rare in the first two decades of life comprising only 3% of newly diagnosed pediatric and adolescent leukemias. We studied the epidemiologic and clinical features of patients with CML diagnosed at younger than 3 years of age and evaluated treatment and long-term outcome. METHOD Data from the International Pediatric I-BFM/CML Registry were retrospectively analyzed using the European LeukemiaNet criteria of the year 2006. Characteristics and treatment outcome of patients

Pyruvate kinase deficiency (PKD) is the most common glycolytic defect leading to chronic nonspherocytic hemolytic anemia (CNSHA). Clinical manifestations of PKD reflect the symptoms and complications of the chronic hemolysis, including anemia, jaundice, bilirubin gallstones due to hyperbilirubinemia, splenomegaly and iron overload. In this study, we report the finding of a 5-months-old Turkish male newborn with moderate CNSHA and PKD. Mutation screening of Pyruvate Kinase Liver/Red (PKLR) gene revealed that the patient carried the known pathogenic variant (PV) c.1456C > T (p.Arg486Trp) and an unreported variant c.1067T > G (p.Met356Arg). Computational variant analysis (CVA) highlighted the deleterious structural effects on the mutant PK enzyme, suggesting its pathogenic role. In this patient, the molecular evaluation of PKD, that allowed the identification of the novel PKLR genotype, coupled with CVA led to the definitive and correct diagnosis of CNSHA.

Aim Umbilical venous catheters are frequently used in the neonatal period. The incidence of umbilical venous catheter-related thrombosis is between 1.3% and 43% in ultrasound scans. This study aimed to determine the incidence and risk of portal vein thrombosis in patients who were hospitalized in the neonatal intensive care unit and underwent umbilical venous catheter insertion. Material and methods Premature infants (≤32 gestational weeks) who were hospitalized in a Level III neonatal intensive care unit and underwent umbilical vein catheter placement between 2016 and 2018, were included in the study. The demographic data, clinical risk factors for thrombosis, number of catheter days, catheter locations, times of detection of thrombosis using Doppler ultrasonography, treatment methods and durations, thrombosis follow-up and examinations were obtained retrospectively from the electronic patient files. Results Ninety-six patients whose complete data could be reached were enrolled in the study. The mean gestational age of the patients was found as 29±2 weeks and the mean birth weight was 1353±369 g. Portal vein thrombosis was detected in 13.5% (n=13) of the patients. Five of the cases of portal vein thrombose were complete occlusion and eight were partial occlusion. All patients with complete occlusion and six patients with partial occlusion were treated with low-molecular-weight heparin for a mean duration of 31±13.8 days. Thrombosis disappeared in 7-120 days in all patients. A thrombophilia mutation was detected in six patients with thrombosis, four of whom had the PAI-1 4G / 5G mutation. Conclusion Portal vein thrombosis which has a significant place among the causes of portal hypertension in childhood, is mostly asymptomatic in the neonatal period and cannot be recognized clinically. It is important to screen and follow up patients with umbilical vein catheters using Doppler ultrasonography in terms of PVT after catheter removal to prevent long-term complications.

Agir adet kanamasi; 7 gunu gecen ya da bir siklusta 80 ml’den fazla kanama olarak tanimlanir. Demir eksikligi anemisinin yani sira; sosyal ve fiziksel aktivitelere katilmada isteksizlik, okula devamsizliklara neden olarak yasam kalitesini azaltir. En sik neden henuz tam olgunlasmamis hipotalamik-hipofizer aksa bagli anovulatuar sikluslar olmakla birlikte, ikinci sik neden altta yatan bir kanama hastaligidir.

WOS: 000426572200002, PubMed ID: 28404539, Objective: The Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate the demographic and disease characteristics of patients and assess the efficacy of a hemoglobinopathy control program (HCP) over 10 years in Turkey. Materials and Methods: A total of 2046 patients from 27 thalassemia centers were registered, of which 1988 were eligible for analysis. This cohort mainly comprised patients with beta-thalassemia major (n = 1658, 83.4%) and intermedia (n = 215, 10.8%). Results: The majority of patients were from the coastal areas of Turkey. The high number of patients in Southeastern Anatolia was due to that area having the highest rates of consanguineous marriage and fertility. The most common 11 mutations represented 90% of all beta-thalassemia alleles and 47% of those were IVS1-110(G->A) mutations. The probability of undergoing splenectomy within the first 10 years of life was 20%, a rate unchanged since the 1980s. Iron chelators were administered as monotherapy regimens in 95% of patients and deferasirox was prescribed in 81.3% of those cases. Deferasirox administration was the highest (93.6%) in patients aged, Ege Children's Foundation; Novartis Pharmaceuticals CorporationNovartis, The authors thank Caglar Serdar, Aylin Gokduman, and Tolga Turgay of Plexus Information Technologies for their website support. The current study and the work presented here are from an Investigator Initiated Trial, which was sponsored by the Ege Children's Foundation and funded by Novartis Pharmaceuticals Corporation.

Introduction: CML is a rare disease in children and adolescents, accounting for 2-3% of leukemia cases in this population. Pediatric CML is more frequent in the 2 nd decade of life but data on adolescents are limited. Only response to treatment has been analyzed in few studies and seems to be poorer in this age cohort. The International Registry of Childhood Chronic Myeloid Leukemia gave us the opportunity to analyze the characteristics and outcome in a large cohort of adolescents. Aims and objectives: To report on clinical features and response to treatment in adolescents (15-18 years of age at diagnosis) with CML in chronic phase (CML-CP). Material and methods: The International Registry of Childhood CML (I-CML-Ped Study, registered at www.clinicaltrials.gov NCT01281735) enrolled patients less than 18 years of age at diagnosis of CML in all phases according to the criteria of the European Leukemia Net (ELN). Data from this registry collected from Jan 2011 - Mar 2021 into the I-CML-Ped Study (Poitiers, France) were retrospectively analyzed. Results: Out of 614 patients (pts) registered in the I-CML-Ped Study, we identified 144 (23.4%) adolescents (15-18 years of age at diagnosis) with sufficient available data. Among them, according to the ELN criteria, 132 (92%), 7 (5%), and 5 (3%) pts presented with CML-CP, accelerated phase (AP), and blastic phase (BP), respectively. The median age of the cohort comprising 132 adolescents with CML-CP was 16.2 years [range, 15-18]. Ratio male/female was 1.75. Splenomegaly was reported in 66% of the pts with a median spleen size of 11.5 cm below the costal margin [range, 1-32]. Hepatomegaly was reported in 31% of the pts with a median liver size of 2.5 cm below the costal margin [range, 1-19]. Pain, asthenia and weight loss were the most frequent symptoms at diagnosis in 35%, 33%, and 20% of pts, respectively. The performance status according to the OMS and Karnofsky scores were 0 and 100% in 81% and 57% of the pts, respectively. At diagnosis, median leukocyte count was 181 G/L [range, 7-820]; median platelet count was 516 G/L [range, 102-2619], and median hemoglobin level was 10.45 g/dL [range, 4-17]. BCR-ABL1 transcript type b3a2 was present in 53% of the assessable pts. Additional chromosomal abnormalities and variants were found in 5% of the pts. 9% and 40% of pts were considered at high-risk according to the ELTS score and to the Sokal score (for pts less than 45 years), respectively. The majority of pts (97%) were treated with imatinib as first line treatment. After 12 months of treatment, in pts with data available, rate of complete cytogenetic response (CCyR) was 74/109 (68%) pts with imatinib first line. Overall, rate of CCyR was 101/109 (93%) pts with imatinib first line [88/109 (81%) pts receiving imatinib only, 13/109 (12%) pts after switching to another TKI, 8/109 (7%) pts did not achieve CCyR]. Median time to achieve CCyR was 8.2 months [range, 2.7-106.7]. The cumulative rate of MMR at month 12 was 40/111 (36%) pts. Overall rate of MMR was 91/111 (82%) pts [72/111 (65%) pts with first line imatinib only; 19/111 (17%) pts with another TKI]. Median time to achieve first MMR was 14.5 months [range, 0.9-63.1]. Out of all patients on first line imatinib, 11/123 (9%) pts progressed: 3/11 pts progressed to AP and 8/11 pts to BP. Further progress to BP was observed in 2 of the 3 pts with AP. BP phenotype was myeloid in 5/10 pts, lymphoid in 3/10 pts and bilineage in 1/10 pts (no data for 1/10 pts). With imatinib first line, deaths occurred in 5/123 (4%) pts, among them 4/5 due to complications associated with hematopoietic stem cell transplantation. With a median follow up of 37 months [range, 0.9-231], the overall survival rate was 89.2% [83.6%; 94.7%] for pts treated with imatinib first line (N = 123). Conclusion: Our results are in line with publications describing adolescents and young adults (AYAs) as a risk population for a poorer treatment outcome: when comparing AYAs (15-29 yrs) to adults (>30 yrs), CCyR and MMR were inferior in AYAs (cumulative CCyR 84% vs 93%, cumulative MMR 75% vs 86%, respectively) [Pemmaraju N et al., Haematologica 2012] and rates of progression to AP and BP were 8.7% in AYAs (16-29 yrs) but only 5.3% and 6.1% in adults (45-59 yrs and >60 yrs, respectively) [Kalmanti L et al. , Ann Hematol. 2013]. Additional research is required in adolescents with CML to shed light on the cause(s) for the observed differences and to further improve the outcome. Disclosures No relevant conflicts of interest to declare.

Background In the adult population with newly diagnosed chronic myeloid leukemia (CML), variant translocations are usually not considered to be impairing the prognosis, whereas some additional cytogenetic abnormalities (ACAs) are associated with a negative impact on survival. Because of the rarity of CML in the pediatric population, such abnormalities have not been investigated in a large group of children with CML. Methods The prognostic relevance of variant t(9;22) and ACAs at diagnosis was assessed in 301 children with CML in the chronic phase who were enrolled in the International Registry for Chronic Myeloid Leukemia in Children and Adolescents. Results Overall, 19 children (6.3%) presented with additional cytogenetic findings at diagnosis: 5 children (1.7%) had a variant t(9;22) translocation, 13 children (4.3%) had ACAs, and 1 had both. At 3 years, for children with a classic translocation, children with ACAs, and children with a variant t(9;22) translocation who were treated with imatinib as frontline therapy, the probability of progression-free survival (PFS) was 95% (95% confidence interval [CI], 91%-97%), 100%, and 75% (95% CI, 13%-96%), respectively, and the probability of overall survival (OS) was 98% (95% CI, 95%-100%), 100% (95% CI, 43%-98%), and 75% (95% CI, 13%-96%), respectively. No statistical difference was observed between the patients with classic cytogenetic findings and those with additional chromosomal abnormalities in terms of PFS and OS. Conclusions In contrast to adults with CML, additional chromosomal abnormalities observed at diagnosis do not seem to have a significant prognostic impact. Cancer 2017;123:3609-16. © 2017 American Cancer Society.

Objective: With increasing survival rates in childhood acute lymphocytic leukemia (ALL), the long-term side effects of treatment have become important. Our aim was to investigate health-related quality of life, depression, anxiety, and self-image among ALL survivors. Materials and Methods: Fifty patients diagnosed with ALL and their siblings were enrolled. The Kovacs Children's Depression Inventory, State-Trait Anxiety Inventory, Offer Self-Image Questionnaire, and Pediatric Quality of Life Inventory (TM) were used for collecting data. ANOVA tests were used to determine if there were any significant differences between groups. Results: ALL survivors had higher depression, more anxiety symptoms, lower quality of life, and more negative self-image when compared to their siblings. Conclusion: Continuous diagnostic and interventional mental health services might be necessary for possible emotional side effects of treatment during and after the treatment. Rehabilitation and follow-up programs should be implemented for children during and after treatment for ALL. Akut lenfoblastik lösemide (ALL) sağkalım oranlarının artmasıyla tedavinin uzun süreli yan etkileri önemli hale gelmiştir. Bu çalışmanın amacı da ALL sağkalanlarında, sağlıkla ilişkili yaşam kalitesi, depresyon, anksiyete ve kendilik imajını incelemektir. Gereç ve Yöntemler: ALL tanısı almış 50 çocuk ile onların aynı sayıdaki sağlıklı kardeşleri çalışmaya dahil edilmiştir. Verileri toplamak için, Kovaks Çocuklar için Depresyon Anketi, Durumluluk-Sürekli Kaygı Envanteri, Offer Kendilik İmajı anketi ve Pediatric Quality of Life InventoryTM kullanılmıştır. Gruplar arası farklar ANOVA yöntemi kullanılarak araştırılmıştır. Bulgular: ALL sağkalanlarının, kardeşlerine göre, depresyon ve anksiyete puanları anlamlı olarak fazladır. Ayrıca, benlik imajlarının daha olumsuz, yaşam kalitelerinin daha düşük idi. Sonuç: ALL tedavisi sırasında ve sonrasında olası duygusal yan etkiler için sürekli tanısal ve girişimsel mental sağlık servisleri gerekli olabilir. Tedavi sırasında ve sonrasında ALL’li çocuklar için rehabilitasyon ve izlem programları uygulanmalıdır.

EgeUn###, Background:Invasive fungal infections, including hepatosplenic fungal infections (HSFI), cause significant morbidity and mortality in children with leukemia. There are not enough data to support for the best approach to diagnosis of HSFI in children, nor for the best treatment.Procedure:In this multicentric study, we assessed the demographic data, clinical and radiologic features, treatment, and outcome of 40 children with leukemia and HSFI from 12 centers.Results:All cases were radiologically diagnosed with abdominal ultrasound, which was performed at a median of 7 days, of the febrile neutropenic episode. Mucor was identified by histopathology in 1, and Candida was identified in blood cultures in 8 patients. Twenty-two had fungal infection in additional sites, mostly lungs. Nine patients died. Four received a single agent, and 36 a combination of antifungals.Conclusions:Early diagnosis of HSFI is challenging because signs and symptoms are usually nonspecific. In neutropenic children, persistent fever, back pain extending to the shoulder, widespread muscle pain, and increased serum galactomannan levels should alert clinicians. Abdominal imaging, particularly an abdominal ultrasound, which is easy to perform and available even in most resource-limited countries, should be recommended in children with prolonged neutropenic fever, even in the absence of localizing signs and symptoms. © 2018 Wolters Kluwer Health, Inc. All rights reserved.

PubMedID: 30300449 Objectives: To evaluate the long-term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion-dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey. Methods: This was a multicenter, prospective cohort study including TDT and SCA patients aged 2-18 years with iron overload (?100 mL/kg of pRBC or a serum ferritin [SF] level >1000 µg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice. Results: A total of 439 patients were evaluated (415 [94.5%] TDT, 143 [32.6%] between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 µg/L (P

Background Chronic myeloid leukaemia (CML) is very rare in children. The aim of the study is to report the experience within the I-CML-Ped study in children and adolescents presenting at diagnosis with advanced phase disease and to describe their characteristics and outcomes. Methods Of 479 children and adolescents enrolled in the international registry for childhood chronic myeloid leukaemia (I-CML-Ped Study; www.clinicaltrials.gov NCT01281735 ), 36 children (7.5%) presented at initial diagnosis with CML in advanced phase according to the European LeukemiaNet criteria. Results Nineteen (4%) patients were diagnosed in accelerated phase (CML-AP), and among the 17 patients (3.5%) diagnosed in blastic phase (CML-BP), 70% presented with lymphoid immunophenotype. Initial treatment of CML-AP/CML-BP consisted of tyrosine kinase inhibitors (TKIs) with or without chemotherapy, leading to complete haematologic response in 33 of 36 (92%) patients. Seventeen patients proceeded to haematopoietic stem cell transplantation. At the last follow-up, 18 of 19 patients with de novo CML-AP are alive in at least major molecular response (MMR) (n = 16), in progression (n = 1) or in molecular relapse (n = 1) and 13 of 17 patients with de novo CML-BP are alive in at least MMR. Five-year overall survival rates are 94% (95% confidence interval [CI]: 66%–99%) and 74% (95% CI: 44%–89%) for patients diagnosed in CML-AP and CML-BP, respectively. Conclusion Children with advanced phase at diagnosis of CML seem to have a better survival rate than that reported for advanced phases evolving under TKI treatment.

Background The outcome of childhood acute lymphoblastic leukemia has improved because of intensive chemotherapy and supportive care. The frequency of adverse events has also increased, but the data related to acute central nervous system complications during acute lymphoblastic leukemia treatment are sparse. The purpose of this study is to evaluate these complications and to determine their long term outcome. Patients and Methods We retrospectively analyzed the hospital reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year period for acute neurological complications. The central nervous system complications of leukemic involvement, peripheral neuropathy, and post-treatment late-onset encephalopathy, and neurocognitive defects were excluded. Results Twenty-three of 323 children (7.1%) suffered from central nervous system complications during acute lymphoblastic leukemia treatment. The majority of these complications (n = 13/23; 56.5%) developed during the induction period. The complications included posterior reversible encephalopathy (n = 6), fungal abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n = 3). Three of these 23 children (13%) died of central nervous system complications, one from an intracranial fungal abscess and the others from intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic and three of them had also developed mental and motor retardation. Conclusions Acute central neurological complications are varied and require an urgent approach for proper diagnosis and treatment. Collaboration among the hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is essential to prevent fatal outcome and serious morbidity.

Introduction:Invasive fungal infections, including central nervous system fungal infections (CNSFI), cause significant morbidity and mortality in children with leukemia,necessitating early diagnosis and treatment. Material and Method: In this retrospective study, the demographic features, diagnostic approach, treatment and outcome of CNSFI in 32 children with leukemia treated in 12 centers in Turkey were evaluated. Results:Of the 32 patients,12 were female,20 were male.The diagnosis was ALL in 23, recurrent ALL in 5, CML in 1, AML in 1; two others had underwent allogeneic bone marrow transplantation. Most (22/32-68,7%) CNSFI episodes occurred during the remission induction phase of the treatment. All recieved broad-spectrum antibiotics for prolonged neutropenic fever. Twenty two had seizures. Six patient had headache, two patient had double vision and headache, one patient had loss of vision and one patient had fascial paralysis. Radiologic imaging was performed for neurologic symptoms and/or prolonged fever in patients with febrile neutropenia after a median of seven days (1-22). Twenty three had multiple and 9 single brain lesions in magnetic resonance imaging. In 15/23 patients, invasive pulmonary fungal infection; in two patients, hepatosplenic fungal infection were detected concurrently. On blood cultures, one patient had geotrichum capitatum fungemia and one had candida albicans fungemia.Galactomannan was positive in 15 (46%) patients. Fourteen patients underwent surgery, in ten microbiological evidence of fungi was confirmed; four aspergillus flavus, one aspergillus niger, one candida, one mucormycosis and one trichoderma longibrachiatum. Hemophagocytosis was observed in three patients. Nine received granulocyte transfusions. Fifteen were transferred to the ICU. Extracorporeal Membrane Oxygenation (ECMO) was used in one patient. Eleven patients (34%) died due to CNSFI at a median of 30 (15-42) days from the beginning of the episode. Out of 21 survivors, seven have permanent neurological sequela. Eighteen patients were recieving antifungal prophylaxis (Fluconazole (16), voriconazole(1) and itraconazole(1), before the CNSFI diagnosis. Thirteen patients received a single antifungal agent, 19 were treated with a combination of antifungals. Median duration of antifungal treatment was 186 (20-730)days. Liposomal amphoterisin-B and voriconazole were the two mostly used agents. Six of the 12 centers participating in the study had a construction going on near their ward at the time of diagnosis. Conclusion: CNSFI is a major cause of mortality and morbidity in children with leukemia and prolonged neutropenic fever. The evaluation of children with leukemia and prolonged neutropenic fever for invasive fungal infections and the addition of empirical antifungal treatment to antimicrobial treatment is important. Cranial imaging in children with leukemia and prolonged neutropenic fever, even in the absence of local sign and symptoms may lead to earlier diagnosis of CNSFI. Disclosures No relevant conflicts of interest to declare.

The EUTOS Long-Term Survival score was tested in 350 children with chronic myeloid leukemia in first chronic phase treated with imatinib and registered in the International Registry for Childhood Chronic Myeloid Leukemia. With a median follow up of 3 years (range, 1 month to 6 years) progression and/or death (whichever came first) occurred in 23 patients. For the entire cohort of patients the 5-year progression-free survival rate was 92% (95% CI: 87%-94%) and the 5-year survival accounting for chronic myeloid leukemia deaths was 97% (95% CI: 94%-99%). Of the 309 patients allocated to low (n=199), intermediate (n=68) and high (n=42) risk groups by the EUTOS Long-Term Survival score, events (progression and/or death) occurred in 6.0%, 8.8% and 26.2%, respectively. Estimates of the 5-year progression-free survival rates according to these three risk groups were 96% (95% CI: 92%-98%), 88% (95% CI: 76%-95%) and 67% (95% CI: 48%-81%), respectively. Differences in progression-free survival according to these risk groups were highly significant (P

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.

Objective: Immune thrombocytopenia (ITP) is a common bleeding disorder in childhood, characterized by isolated thrombocytopenia. The International Working Group (IWG) on ITP recently published a consensus report about the standardization of terminology, definitions, and outcome criteria in ITP to overcome the difficulties in these areas. Materials and Methods: The records of patients were retrospectively collected from January 2000 to December 2009 to evaluate the data of children with ITP by using the new definitions of the IWG. Results: The data of 201 children were included in the study. The median follow-up period was 22 months (range: 12-131 months). The median age and platelet count at presentation were 69 months (range: 7-208 months) and 19x10(9)/L (range: 1x10(9)/L to 93x10(9)/L), respectively. We found 2 risk factors for chronic course of ITP: female sex (OR=2.55, CI=1.31-4.95) and age being more than 10 years (OR=3.0, CI=1.5-5.98). Life-threatening bleeding occurred in 5% (n=9) of the patients. Splenectomy was required in 7 (3%) cases. When we excluded 2 splenectomized cases, complete remission at 1 year was achieved in 70% (n=139/199). The disease was resolved in 9 more children between 12 and 90 months. Conclusion: Female sex and age above 10 years old significantly influenced chronicity. Therefore, long-term follow-up is necessary in these children. Gereç ve Yöntemler: ITP’li hastalarımıza ait kayıtlar Ocak 2000’den Kasım 2009’a kadar, geriye yönelik olarak, IWG’nin yeni kriterleri kullanılarak değerlendirilmek üzere toplandı. Bulgular: İki yüz bir çocuğun verileri çalışmaya dahil edildi. Ortanca takip süresi 22 ay (12-131 ay) idi. Başvuru anında ortanca yaş ve trombosit sayısı, sırası ile 69 ay (7-208 ay) ve 19x109/L (1-93x109/L) idi. Hastalığın kronikleşmesi açısından iki risk faktörü saptadık: Kız cinsiyet (OR=2,55, CI=1,31-4,95) ve yaşın 10’dan büyük olması (OR=3,0, CI=1,5-5,98). Hayatı tehdit edici kanama, hastaların 5%’inde (n=9) görüldü. Splenektomi yapılması,7 hastada (3%) gerekti. İlk bir yılda splenektomi yapılan 2 hasta göz ardı edildiğinde, tam remisyon (CR) 70% (n=139/199) hastada görüldü. Hastalık, kronik ITP’li olguların 9’unda (%15; 9/60) daha tanıdan itibaren12 ile 90 ay içerisinde düzeldi. Sonuç: Kız cinsiyet ve yaşın 10’dan büyük olması, kronikleşmeyi belirgin olarak etkiledi. Ancak bu çocuklarda uzun sureli takip gereklidir

Introduction: CML is rare in the first two decades of life comprising only 3% of pediatric and adolescent leukemias. The overall annual incidence is approximately 1 per million children and adolescents and it increases with age (median: 12 yrs, range: 1-18) resulting in an extreme rarity of children affected in the first years of life. Data regarding the clinicopathologic characteristics and response to therapy of childhood CML diagnosed at age Aims and objectives: We studied the epidemiologic and clinical features of patients(pts) with CML Material and Methods: Data from pediatric CML pts (age at diagnosis 0-18 yrs) registered from 2010 until 2017 into the International Pediatric CML Registry (Poitiers, France) under the umbrella of the I-BFM Study Group were retrospectively analyzed. Characteristics and treatment outcome of pts Results: 22/479 pts (4.6%, ratio male/female: 14/8) were enrolled with a median age of 22 months (10-34) and a median weight and height were 9.3 kg (8.1-15.5) and 78 cm (73-98), respectively. The median time period from the first symptoms until final diagnosis was 21 days (2-182). Median spleen size was 12 cm (2-20) and median liver size was 3 cm (2-6) below the costal margins. Major complains and symptoms comprised asthenia (30%), fever (30%), abdominal pain (20%), extramedullary signs (14%), hemorrhage (5%), and weight loss (5%). Median WBC, Hb and platelet counts were 154 600/µl (23 000-892 000), 8.7 g/dl (5,6-11,5) and 311 000/µl (51 000-1 820 000), respectively. All pts underwent BM aspiration but, BM biopsy was performed only in 8/22 children. Philadelphia chromosome and BCR-ABL1 gene rearrangement were detected by cytogenetic and/or molecular techniques (FISH and RQ-PCR). In only 2 (9%) children, additional chromosomal abnormalities were detected by cytogenetics classifying one patient in accelerated phase. Overall 19/22 (86%) children were diagnosed in chronic phase and the remaining 3 pts were in advanced phase (CML-AP: n= 2, CML-BP: n= 1). Median follow-up of the cohort was 78 months (7-196). Treatment: 21/22 pts initially received imatinib at the recommended dose of 260-300 mg/sqm/day while one child received IFN + ARA-C. Imatinib was changed to either dasatinib (n= 5) or nilotinib (n= 1) in 6 children (29%). Thus, 15 pts continued on imatinib. During follow-up, 9/22 (41%) pts underwent HSCT including 2 pts after switching to dasatinib. Molecular response: Major molecular response (MR) was achieved in 10/21 (48%) children on TKI. One child (1/21) on TKI was not followed for MR, but he developed complete cytogenetic remission 4 mo after imatinib treatment. The remaining cohort (6/22; 27%) is alive on TKI without major MR with a median follow-up of 77 m (7-186) and 5/22 (23%) achieved complete MR following HSCT. Adverse effects (AE): 194 AE episodes were reported in 18/22 (82%) pts. Most frequently observed AEs were hematologic (20%), gastrointestinal (16%), infectious (14%), musculoskeletal (14%), skin (12%), metabolic (6%), and HSCT-related (GvHD, 5%). Less frequently AEs comprised psychological (3%), edema (3%), tooth development delay (2%), allergic (2%), neurologic (PRESS syndrome,1%), and renal colic (1%). At last follow up, assessment of puberty status revealed that the majority of children were in Tanner stage 1 or 2 (17/22, 77%). Among these, 7 were >10 years old and showed puberty delay, while pubertal development was normal in the remaining 5/22 pts. Data on growth and development was available in 15/22 (68%) children. The majority had experienced decline of height (93%) and weight (73%). In 4 (27%) and 2 (13%) pts, respectively, measurements were found below the 3rd-10th percentiles. Delta z-score analysis for height and weight revealed that the z-scores in total 3 pts were below -2. Survival: 21/22 (95%) children are alive while one patient died of GvHD. Two pts' last molecular status is unknown. 7/19 pts (37%) are in molecular CR following HSCT and the other 12/19 (63%) are still on TKI. Out of these, 3/12 pts achieved durable CMR with TKI (PCR negative) while the remaining 9/12 pts show either fluctuating (n= 3 ) or no major MR (n= 6). Conclusion: This report demonstrates for the first time the efficacy and long term side effects of upfront imatinib in the so far largest cohort of children with CML diagnosed at very young age. Disclosures Kalwak: Sanofi: Other: travel grants; medac: Other: travel grants.

Catheter-associated bloodstream infections (CABSIs) are common complications encountered with cancer treatment. The aims of this study were to analyze the factors associated with recurrent infection and catheter removal in pediatric hematology-oncology patients. All cases of CABSIs in patients attending the Department of Pediatric Hematology-Oncology between January 2008 and December 2010 were reviewed. A total of 44 episodes of CABSIs, including multiple episodes involving the same catheter, were identified in 31 children with cancer. The overall CABSIs rate was 7.4 infections per 1000 central venous catheter (CVC) days. The most frequent organism isolated was coagulase-negative Staphylococcus (CONS). The CVC was removed in nine (20.4%) episodes. We found that hypotension, persistent bacteremia, Candida infection, exit-side infection, neutropenia, and prolonged duration of neutropenia were the factors for catheter removal. There were 23 (52.2%) episodes of recurrence or reinfection. Mortality rate was found to be 9.6% in children with CABSIs. In this study, we found that CABSIs rate was 7.4 infections per 1000 catheter-days. CABSIs rates in our hematology-oncology patients are comparable to prior reports. Because CONS is the most common isolated microorganism in CABSIs, vancomycin can be considered part of the initial empirical regimen.