Search

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening hyperinflammation syndrome emerging after COVID-19. The serum delta neutrophil index (DNI) reflects the fraction of circulating immature granulocytes and is evaluated in infection and inflammation. The aim of this study is to evaluate the usefulness of DNI as a diagnostic marker in patients with MIS-C and to assess its role in determining the severity of MIS-C. This retrospective, observational study included 83 patients with MIS-C and 113 patients with COVID-19, and 102 healthy controls. C-reactive protein (CRP), the absolute neutrophil count (ANC), absolute lymphocyte count (ALC), DNI, and the platelet count were recorded. The DNI levels were 4.60 ± 5.70% in the MIS C group, 0.30 ± 0.99% in the COVID group, and 0.20 ± 0.56% in the control group (p < 0.001). According to the severity of MIS-C, the DNI level was found to be 1.22% in mild MIS-C, 4.3% in moderate MIS-C, and 5.7% in severe MIS-C. There was a statistically significant correlation between DNI levels and the severity of MIS-C. The cutoff value of DNI for predicting MIS-C was 0.45%. In the analysis of the diagnostic performance of DNI compared with CRP, ANC, ALC and platelet counts, sensitivity, specificity, positive predictive value, and negative predictive value were found to be 79.5%, 97.1%, 95.7%, and 85.3%, respectively.Conclusions: The delta neutrophil index was identified as a diagnostic marker for MIS-C such as ANC, ALC, platelet count, and CRP. DNI levels in hemogram analysis may guide clinicians in determining the diagnosis and severity of MIS-C. What is Known: • Although CRP, sedimentation, ALC, ANC, platelet count, sodium, and albumin are used as first step tests, there is no specific laboratory marker used in the diagnosis of MIS C. • The serum delta neutrophil index (DNI) reflects the fraction of circulating immature granulocytes and is elevated in infection and inflammation. What is New: • DNI is a promising and easily accessible marker that can be used with other markers in the diagnosis and determines the severity of MIS C. • DNI is an easily accessible, inexpensive, and dynamic marker and its levels in simple hemogram analysis will guide pediatricians in determining the diagnosis and severity in MIS C.

Objective The aim of this study was to explore adolescent survivors' views and expectations about long-term follow-up care. Methods Semi-structured, in-depth interviews were conducted with 16 adolescent survivors of childhood acute lymphoblastic leukaemia. Survivors who had completed treatment at least 2 years ago were involved in the study. Interviews were audio-recorded and transcribed verbatim. An inductive thematic approach was used to analyse the data. Results Four main themes and sub-themes were identified from the analysis as follows: information needs with three sub-themes 'long-term follow-up, healthy life and social life', support needs with three sub-themes 'psychosocial (peer relations etc.), school related and social-emotional (fear of relapse, body image, self-esteem, etc.)', perceived benefits with two sub-themes 'social-emotional and related to long-term follow-up' and perceived barriers 'medical-hospital related and social life'. Conclusions Adolescent survivors mainly need support in terms of psychosocial aspects: self-esteem-body image, school, peer relations and social activities during follow-up. Identified barriers related to follow-up were school absence and not able to participate social activities. Adolescents specify health promotion approaches as benefits aspects of follow-up. The findings of this study will guide nurses in the long-term follow-up care of adolescent survivors of acute lymphoblastic leukaemia and provide an opportunity to plan individualised follow-up care.

Introduction: Biological drugs are currently used for the treatment of chronic inflammatory, autoimmune, and neoplastic diseases. With their expanding indication spectrum and increasing use, hypersensitivity reactions to these drugs are also becoming more frequent. The present study aimed to report the incidence and the features of such reactions in pediatric patients using biologicals for the treatment of various diseases. Methods: The medical records of pediatric patients treated with biological agents between October 1, 2011 and August 31, 2019 were reviewed and adverse reactions were evaluated retrospectively. Results: During the study period, 211 patients (116 boys, 55%) used 21 different biological drugs for the treatment of various diseases. Their median age at the time of the first treatment was 139.9 (IQR: 92.2–187.8) months. Hematologic-oncologic diseases were the most common indication for biological therapy (97/211; 46.0%), followed by rheumatologic diseases (82/211; 38.9%). Of the 211 patients, 14 (6.64%) experienced reactions to biological drugs. The most common culprit agent was rituximab (57.1%). Most of the patients (85.7%) had a history of reactions either during the infusion or within 1 h after taking the drug. Five patients underwent desensitization to the culprit drug, while 7 other patients continued treatment with a reduced dose/infusion rate or premedication. Also 1 patient continued to take the drug without any additional treatment. Conclusion: It was reported that 6.64% of the patients who received biologic drug therapy for various reasons in our hospital had hypersensitivity. The most common culprit agent was rituximab, and most of the reactions were immediate reactions.

Objective Compared with other cytogenetic acute myeloid leukemia (AML) groups, patients with core-binding factor AML (CBF-AML) are considered as a favorable AML risk group based on their high remission rate and survival probabilities. However, up to 30-40% of these patients can still relapse after standard intensive induction and consolidation chemotherapy. Methodology From 2004 to 2020, 147 AML patients reviewed. Ten of 147 patients were followed up with t(8;21) chromosomal anomaly. The t(8;21)(q22;q22) was detected by reverse transcription polymerase chain reaction (RT-PCR) and/or floresan in situ hibridizasyon (FISH). We analyzed patients’ demographic data: sex, white blood cell count at diagnosis, central nervous system status, additional cytogenetic anomaly and recurrence rates, stem cell transplant status and survival rates. Results Two of 10 patients were female. The median age was 10 years (3-17 years). Median followup was 36 months (2-114 months). The mean white blood cell count of 10 patients was 21.5 (× 109/l) at diagnosis. One out of 10 patients had granulocytic sarcoma and 2 had central nervous system involvement. Additional cytogenetic anomalies were detected in 90% of the patients, of which 2 relapsed and 3 died. One patient received hematopoietic stem cell transplantation and died because of HSCT complications. Conclusion Recent studies show that CBF-AML includes different groups with different clinical outcomes. We found that 50% of our patients achieved complete remission and 50% experienced relapsed disease or death. After we were able to monitor the t(8;21) level with RT-PCR, we diagnosed relapsed disease in 1 patient with additional cytogenetic anomaly. RT-PCR is essential for optimal handling of these patients to predict patients’ relapse risk and to detect minimal residual disease.

Objective Our study aims to evaluate the patients’ immunity regarding childhood vaccination after leukemia treatment and determine the vaccines that require additional doses. Methodology Sixty-six patients who were followed up with the diagnosis of ALL and AML between 2013 and 2016 were included in our study. The patient's gender, age at diagnosis, leukemia type, leukemia risk groups, vaccination status before chemotherapy (CT) and serologies of hepatitis A, hepatitis B, varicella, measles, rubella, mumps at the end of CT were recorded. Results At the end of the treatment, loss of protective antibody response against hepatitis A (47.4%), hepatitis B (68.2%), varicella (64.2%), measles (45.5%), rubella (43.9%), and mumps (50%) vaccines were shown. Loss of protective antibodies against hepatitis A (66.7%), hepatitis B (100%), varicella (100%), measles (100%), rubella (91.7%), and mumps (91.7%) in high-risk ALL patients was higher than patients in standard-intermediate risk ALL. Conclusion Loss of humoral immunity against hepatitis A, hepatitis B, varicella, MMR was shown in patients with leukemia at the end of the treatment. Due to the significant decrease in hepatitis B and MMR protective antibodies in the high-risk group, we recommend patients with leukemia who have completed chemotherapy to be vaccinated with hepatitis B vaccine three months and MMR vaccine six months after the treatment.

SARS-CoV-2 primer olarak solunum yolu enfeksiyonuna neden olmakla birlikte hematopoietik ve immun sistemlerini de etkileyebilmektedir. Enfekte olan hastalarda, lenfositler, notrofiller, monositler ve trombositlerde kantitatif ve kalitatif degisiklikler bildirilmektedir. Bu degisiklikler ile hastaligin siddeti arasinda iliski oldugu da gosterilmistir. Lenfopeni, SARS-CoV-2 ile enfekte eriskin hastalarda en sik gorulen bulgu iken cocuklarda cok daha az gorulmektedir. Siddetli enfeksiyonu olan hastalarda lokositoz saptanabilir, hafif-orta siddette enfeksiyonu olan hastalarda ise lokositoz daha nadirdir. Klinik ile uyumlu olarak trombositopeni veya trombositoz da gorulebilmektedir. Hastalarin periferik yaymalarinda ozellikle notrofil ve trombositlerde displastik morfolojik degisikler saptanabilir.

INTRODUCTION Invasive fungal infections (IFIs) are significant causes of morbidity and mortality in leukemia patients. This study investigated antifungal treatment and prophylaxis features according to leukemia risk groups and treatment phases in pediatric acute lymphoblastic leukemia (ALL) patients who received Berlin-Frankfurt-Munster-based protocols. MATERIALS AND METHODS We retrospectively examined ALL patients' data between the ages of 1 and 18 and treated them with Berlin-Frankfurt-Munster-ALL protocols between June 2013 and December 2016. RESULTS A total of 446 febrile neutropenic attacks in 85 children were evaluated. Seventy-two patients received antifungals in 151 infection attacks, while 13 patients did not receive any antifungal treatment during chemotherapy. Empirical, preemptive, or proven treatments were given to 74.8%, 21.2%, and 4% of patients, respectively. The frequency of antifungal therapy increased linearly and significantly from the standard-risk group to the intermediate-risk (IR) group, high-risk (HR) group, and relapsed group. IR patients needed more antifungal therapy while receiving induction, whereas HR patients needed more throughout the induction and HR consolidation blocks than other phases. During induction, IR patients received antifungal therapy similar to HR patients' treatment in the induction and HR consolidation blocks. CONCLUSIONS Antifungal therapy requirements increased as the severity and intensity of chemotherapy increased for all leukemia risk groups. The requirement of antifungal therapy for IR patients receiving induction was similar to that of HR patients; further studies are needed to evaluate the potential advantages of using primary antifungal prophylaxis in IR patients.

ObjectiveAcute lymphoblastic leukemia (ALL) is the mostcommon childhood cancer. In addition to complaintssuch as fatigue, bruising, bleeding, fever of unknownorigin, non-specific bone, and joint pain may be thefirst sign. The purpose of this study, to determine thedemographic characteristics, laboratory findings, andtreatment results of patients presenting with bone andjoint pain and to compare with ALL patients withoutbone joint pain, and to evaluate the radiologicalfindings of patients with bone joint pain.Material and MethodsData of 163 patients who were diagnosed, treatedand followed up with the diagnosis of ALL in theUniversity of Health Sciences, Ankara City Hospital,Department of Pediatric Hematology and Oncologybetween January 2013 and June 2018 were evaluatedretrospectively. A total of 33 patients presented withbone and joint complaints. The demographic features,laboratory findings, and recent status of all patientswere examined retrospectively.ResultsThere was no statistically significant differencebetween the patients with bone and joint complaints(Group I) and without bone and joint complaints (GroupII) in terms of age, gender, and immunophenotyping(p> 0.05). The median white blood cell was lower, andthe platelet value was higher in Group I at diagnosis (p, AmaçAkut lenfoblastik lösemi (ALL) en sık görülen çocuklukçağı kanseridir. Çabuk yorulma, morarma, kanama,sebebi bilinmeyen ateş gibi şikayetlerin yanı sıra;non-spesifik kemik ve eklem ağrısı ilk başvuru bulgusuolabilmektedir. Bu çalışmanın amacı; kemik veeklem ağrısı şikayeti ile başvuran hastaların demografiközelliklerini, laboratuvar bulgularını ve tedavi sonuçlarınıbelirlemek, kemik eklem ağrısı olmayan ALLhastaları ile karşılaştırmak ve kemik-eklem ağrısı olanhastaların radyolojik bulgularını değerlendirmektir.Gereç ve YöntemSağlık Bilimleri Üniversitesi Ankara Çocuk Sağlığı veHastalıkları Çocuk Hematoloji Onkoloji Eğitim AraştırmaHastanesi Pediatrik Hematoloji Bilim Dalında,Ocak 2013 – Haziran 2018 tarihleri arasında ALL tanısıalan 163 hastanın dosyası retrospektif olarak incelendi.Kemik ve eklem yakınmaları ile başvuran 33hasta tespit edildi. Kemik eklem yakınması olan hastalar;Grup I ve kemik eklem yakınması olmayan hastalar;Grup II olarak sınıflandırıldı. Tüm hastaların tanısırasındaki demografik özellikleri, laboratuvar bulgularıve son durumları geriye dönük olarak incelendi.BulgularGrup I ve Grup II’ de yer alan hastalar arasında yaş,cinsiyet, immünfenotiplendirme açısından istatistikselolarak anlamlı fark bulunmadı (p>0,05).Grup I’de; ortancabaşvuru beyaz küre değeri düşük ve trombositdeğeri ise daha yüksek saptandı (p

Amaç: Hemofili A hastalarında kanamaların önlenmesi ve kas-iskelet sistemi fonksiyonlarının korunması amacıyla faktör VIII (FVIII) ile profilaksi önerilmektedir. Farmakokinetik (FK) verilerle düzenlenen profilaksi, kanamalardan korunmada ve tedavi maliyetinin azaltılmasında günümüzdeki en başarılı stratejidir.Gereç ve Yöntemler: Bu çalışmada Bayesian yöntemi kullanan, myPKFiT web erişimli program aracılığı ile FVIII FK verileri hesaplanan 17 ağır hemofili A (ortanca yaş 11.5 yıl, ortanca kullandıkları faktör miktarı 25 U/kg) hastası sunuldu. Bulgular: Çalışmaya dahil edilen hastaların ortalama FVIII yarılanma ömrü 9.1 saat (min-max: 6.8-11.4), ortalama FVIII klerensi 4.7 ml/saat/kg (min-max: 2.6-6.8), ortalama FVIII’in

We aimed to evaluate the impact of pretreatment folate and vitamin B12 deficiencies on the frequency of complications and peripheral blood recovery, in children with acute lymphoblastic leukemia (ALL). Pre-induction serum folate and vitamin B12 levels of 88 newly diagnosed ALL patients were evaluated retrospectively. Folate 1.0 × 109/L and platelet count > 100 × 109/L at 33rd day of chemotherapy were also evaluated. Folate or vitamin B12 deficiencies were observed in 21 (23%) and 40 (45%) children, respectively. Peripheral blood counts, complications rates, and transfusion needs were not statistically different between deficient and normal level groups during induction. The number of febrile days, though not statistically significant, was higher in the both deficient groups. Seventeen of 40 (42.5%) patients with vitamin B12-deficient and 12 of 21 (57.1%) folate-deficient patients experienced at least one episode of FN during induction. FN was more common in folate-deficient group, but that was not statistically significant. Complete peripheral blood recovery at 33rd day of induction was seen in 40% in the vitamin B12-deficient group and 28.6% in folate-deficient group. Peripheral blood recovery rate at day 33 was also similar in both deficient and normal level groups. Although pre-induction low serum levels of vitamin B12 and folate did not have statistically significant impact on disease-/treatment-related complications and peripheral blood recovery at induction, the frequency of FN and number of febrile day were higher in both deficiencies and folate-deficient patients, respectively.

The aim of the study was to analyze the characteristics of posterior reversible encephalopathy syndrome (PRES) cases treated at 10 different institutions in our country. Fifty-eight patients diagnosed with PRES were included in this study. The data of PRES cases from 10 departments of pediatric hematology/oncology were analyzed. The mean age of the patients at the time of diagnosis of PRES was 8.95 +/- 3.66 years. Most patients (80.4%) had a primary diagnosis of acute leukemia. Patients received chemotherapy (71.4%) and/or used steroids within 14 days before the diagnosis of PRES (85.7%). Hypertension was found in 83.9% of the patients. Twenty-six patients had infections and 22 of them had febrile neutropenia. The most common electrolyte disorders were hypocalcemia, hypomagnesemia, and hypopotassemia. Six patients had tumor lysis syndrome and 4 had inappropriate antidiuretic hormone syndrome. Magnetic resonance imaging was used for diagnosis in all patients. The most commonly involved regions by magnetic resonance imaging were occipital (58%), parietal (51%), and frontal lobes (45%), respectively. Twenty-five patients required intensive care and 7 patients were intubated. In conclusion, PRES may develop during the follow-up and treatment of hematological diseases. In addition to steroid and intense combined chemotherapies, immunosuppressive agents and hypertension are also factors that may be responsible for PRES.

In this study, we aimed to investigate changes in calcium (Ca) metabolism in hemophilia patients (PWH). We also aimed to investigate the importance of diagnosis and treatment of factors impairing calcium metabolism and the significance of early diagnosis and prophylaxis with respect to these subjects. For all patients, serum calcium, phosphorus, alkaline phosphatase, 25 hydroxy vitamin D (25-OHD), parathormone (PTH), and calcitonin levels were evaluated. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry. Low BMD scores and 25-OHD deficiency were observed in 29 (74.4%) and 34 (87.2%) patients, respectively. Prophylaxis of PWH did not differ significantly in terms of 25-OHD levels and BMD scores. Patients in the prophylaxis group had significantly higher PTH levels (P=0.042). A negative correlation was found between PTH measurements and Z-score (P=0.008). In summary, our findings, with a small number of PWH in our study group, suggest that biochemical markers of bone turnover may be used to detect bone loss. Follow-up through annual BMD measurements coupled with appropriate exercise programs could be recommended.

Objective: This cross-sectional study aimed to reveal possible hemostatic disorders in patients referred to the Pediatric Hematology Department due to the prolongation of the prothrombin test (PT) or activated partial thromboplastin test (aPTT). Methodology: In this study, patients aged 0-18 years without known hematologic disease were referred to investigate the incidental prolonged PT and/or aPTT were evaluated. Mixing studies were performed in patients with continued PT/aPTT prolongation in the control examinations. Coagulation factor activities were analyzed in patients with improvement in mixing study. Antiphospholipid antibodies were studied in patients whose results did not improve with mixing studies. Results: Coagulopathy was found in 30% of 103 patients. Lupus anticoagulant positivity was found in two patients (1.9%). The most common factor (F) deficiencies were FVII deficiency (10.6%), FXI deficiency (7.8%), FXII deficiency (7.8%), FV deficiency (0.9%), FVIII deficiency (0.9%), fibrinogen and FVII deficiency (0.9%) and von Willebrand factor (vWF) deficiency (0.9%). Coagulopathy was more common in patients with bleeding disorders in their families, and this difference was statistically significant. Conclusion: In our study, mild factor deficiencies were more common than expected. Coagulation factor deficiencies can be seen in the patients without any finding of physical examination, personal and family histories. There is often no evidence of bleeding in mild factor deficiencies, and the clinical significance is unknown. We recommend using PT and aPTT as screening tests, especially before a major surgical intervention is performed.

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.

Azik, Fatih/0000-0001-5715-4244 WOS: 000480419100010 PubMed ID: 30470618 Objective: Immune thrombocytopenic purpura (ITP) is the most common cause of acquired thrombocytopenia children. The aim of this retrospective study is to describe presenting features and clinical characteristics of ITP and evaluate clinical course, treatment modalities, and complications and determine the effects of preceding infection history, age, gender, treatment modality, and admission platelet count on chronicity. Method: Two hundred and eleven patients who were diagnosed ITP and followed-up in Department of Pediatric Hematology, Ankara Children Hematology Oncology Education and Research Hospital between January 2008 and September 2012 were included. Age of the patients, gender, date of admission, date of diagnosis, complaint in the application, previous infection and laboratory tests were recorded. Results: Mean age of the patients on diagnosis was 5.4 +/- 4.1 years. The female/male ratio was 1.03. The clinical courses were determined as acute or chronic in 72% and 28% of patients respectively. Mean age at diagnosis was significantly higher in chronic ITP (p < 0.01). Chronic course was significantly higher in female patients (p < 0.05). The most frequent complaint was bruises on the skin (68%). The most common physical examination findings were petechiae, purpura and ecchymosis (89%). Patients with a history of past infection (53.6%) and who had serologically positive infection (15.6%) frequently had acute course (p < 0.01). The most common serologically positive infection was Rubella. The mean platelet count was significantly higher in chronic ITP (p < 0.01). In the initial treatment of patients admitted in the acute phase, megadose methylprednisolone (MDMP) was used in 31% of patients, intravenous immune globulin (IVIG) in 55% of patients and anti-D in 2% of patients while 12% did not receive any treatment. There were no significant differences between the recurrence rate and treatment modality (p > 0.05). Conclusion: In our study, in females and in patients without any history of past infection, platelet count >20 x 10(9) /L and initial diagnosis age > 10 years were found to increase the probability of chronic disease, which is compatible with the literature. Copyright (C) 2018, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC.

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

Acquired aplastic anemia (AAA) is a rare and potentially life threatening disorder. We retrospectively compared the outcomes of 29 children with AAA who received immunosuppressive therapy (IST) or underwent hematopoietic stem cell transplantation (HSCT). Median age at diagnosis was 9.0 years (range, 2-18 years) and median follow-up period was 36 months (range, 3-108 months). Viral infection associated/post hepatitis AAA was in 6 patients (20.6%). According to the initial laboratory findings, 8 patients were classified as very severe AA (vSAA), 8 as severe AA (SAA), and 13 patients as transfusion-dependent moderate AA (MAA). Out of 13, 5 transfusion-dependent MAA patients progressed SAA in median one month (range, 1-5 months), another 6 MAA patients developed remission or became transfusion free during follow-up. Eight patients underwent upfront matched family donor (MFD) HSCT at median 6 months (range, 1-9 months) and achieved complete response (100%). Fifteen cycles of IST were given to 10 (34%) patients lacking MFD at median 3 months (range, 2-6 months). Fifty percent of patients had complete/partial response after IST protocol. Three patients who were unresponsive to IST, proceeded to alternative donor HSCT, in 2nd or 3rd year after the diagnosis and only 1 patient was sustained remission. Several drugs such as mycophenolatemofetil, high-dose cyclophosphamide, levamisole and eltrombopag have been investigated in order to improve the outcome of patients with AAA. Early intervention in AAA patients results in significantly better outcomes.

Background: Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by the abnormal expansion of clonal lymphoblasts in the bone marrow (BM). The behavior of malignant lymphoblasts is not only dependent on their genomic abnormalities but also, on their complex and reciprocal relationships with their local niche. BM microenvironment is a dynamic network of growth factors, cytokines, and stromal cells, providing a permissive environment for leukemogenesis and progression. Despite some evidence about the implication of the bidirectional interaction between mesenchymal stromal cells (MSCs) and leukemic cell on growth and survival, it is still largely unknown. Although an increasing number of studies are reporting on the expression of specific genes in leukemic cells-interacting MSCs, gene expression profiling in cocultured MSCs (with respect to mono culture conditions) has not been done on a transcriptome-wide basis. Taking all this into consideration, we have established cocultures between BM-derived MSCs and the leukemic mononuclear cells and performed gene expression profile (GEP) studies on the MSC population to determine those deregulated genes due to the coculture condition with respect to MSCs in mono culture. Methods: Primary MSCs from BM samples of healthy donors (n=4) and pediatric pre-B ALL patients (n=4) were isolated and expanded and mononuclear cells were, also, isolated from patients peripheral blood. At passage 2, healthy/patient (h/p) MSCs were cocultured with the leukemic cells for 72 hours and subsequently subjected to GEP analyses. RNA isolated from h/pMSCs and biotinylated amplified RNA was synthesized. For the hybridization HG-U133 Plus, 2.0 GeneChip oligonucleotide arrays (Affymetrix) was used. Raw microarray data were processed into expression values through the Affy package in R. RMA (robust multi-array average) algorithm was used for preprocessing. The linear regression model package LIMMA (Linear Models for Microarray Data) was used to identify significant differential expression of genes (DEGs) compared to h/pMSCs after coculture with MSCs from the same origin in mono culture. Minimum 1.5 fold change and p-value < 0.001 were defined as the threshold. Functional enrichment, gene network and pathway analysis, were performed on selected sets of genes after differential expression analyses using two bioinformatics tools: DAVID Bioinformatics Resources 6.8 and WebGestalt 2019. Results: We identified 293 DEGs when analyzing pMSC samples vs. hMSC in coculture condition and 853 DEGs of pMSC vs. hMSC analyze in mono culture condition and only 15 DEGs common in both group. According to the result of functional enrichment analysis of pMSC vs. hMSC in coculture condition, 29 gene ontology (GO) term biological process including (top five) apoptotic process, axon guidance, regulation of JNK cascade, cell-cell adhesion and protein phosphorylation and 4 KEGG pathways of DEGs including axon guidance, FoxO signalling pathway, Wnt signalling pathway and signalling pathways regulating pluripotency of stem cells were determined. Comparing pMSC vs. hMSC in mono culture condition, 292 GO term biological process including extracellular matrix organization, skeletal system development, angiogenesis and signal transduction and 43 KEGG pathways of DEGs including pathways in cancer, TGFß signalling pathway, ECM-receptor interaction, p53 signalling pathway and PI3-Akt signalling pathway were determined.Five genes with upregulated expression after coculture (COL18A1, EFNA5, MAP3K8, CASP1, IGF1R) and after mono culture (MMP1, CXCL1, IL1B, PCDH10, CXCL6) were identified. Conclusions: Deregulated genes especially after coculture condition in axon guidance and ephrin receptor-mediated signalling pathway of which the importance is not yet understood in cancer microenvironment including EPHB1, ephrinA5, ephrinB3, p21 activated kinase 2 (PAK2), and ROBO3 showed highly differential expression pattern between pMSCs and hMSCs. This is the first report indicating the importance of axon guidance genes as a result of interaction between MSCs and leukemic cells. The elucidation of deregulated mechanisms and pathways provides new molecular insights to the contribution of these cells to ALL pathophysiology and understanding cross talk between these cells may lead to found new therapeutic targets. Disclosures No relevant conflicts of interest to declare.

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.