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Pyruvate kinase (PK) is a key enzyme of anaerobic glycolysis. The genetic heterogeneity of PK deficiency (PKD) is high, and over 400 unique variants have been identified. Twenty-nine patients who had been diagnosed as PKD genetically in seven distinct paediatric haematology departments were evaluated. Fifteen of 23 patients (65.2%) had low PK levels. The PK:hexokinase ratio had 100% sensitivity for PKD diagnosis, superior to PK enzyme assay. Two novel intronic variants (c.695-1G>A and c.694+43C>T) have been described. PKD should be suspected in patients with chronic non-spherocytic haemolytic anaemia, even if enzyme levels are falsely normal. Total PKLR gene sequencing is necessary for the characterization of patients with PKD and for genetic counselling., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Acute kidney injury (AKI) is a common complication of hematopoietic stem cell transplantation (HSCT) with increased mortality and morbidity. Understanding the risk factors for AKI is essential. This study aimed to identify AKI incidence, risk factors, and prognosis in pediatric patients post-HSCT., Methods: We conducted a retrospective case-control study of 278 patients who were divided into two groups: those with AKI and those without AKI (non-AKI). The groups were compared based on the characteristics and clinical symptoms of patients, as well as post-HSCT complications and the use of nephrotoxic drugs. Logistic regression analysis was employed to identify the risk factors for AKI., Results: A total of 16.9% of patients had AKI, with 8.5% requiring kidney replacement therapy. Older age (OR 1.129, 95% CI 1.061-1.200, p < 0.001), sinusoidal obstruction syndrome (OR 2.562, 95% CI 1.216-5.398, p = 0.011), hemorrhagic cystitis (OR 2.703, 95% CI 1.178-6.199, p = 0.016), and nephrotoxic drugs, including calcineurin inhibitors, amikacin, and vancomycin (OR 17.250, 95% CI 2.329-127.742, p < 0.001), were identified as significant independent risk factors for AKI following HSCT. Mortality rate and mortality due to AKI were higher in stage 3 patients than those in stage 1 and 2 AKI (p = 0.019, p = 0.007, respectively). Chronic kidney disease developed in 1 patient (0.4%), who was in stage 1 AKI (2.1%)., Conclusions: AKI poses a serious threat to children post-HSCT, leading to alarming rates of mortality and morbidity. To enhance outcomes and mitigate these risks, it is vital to identify AKI risk factors, adopt early preventive strategies, and closely monitor this patient group., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Herbaspirillum species are nonfermenting, aerobic, helical or curved, Gram-negative bacteria belonging to the class Betaproteobacteria, order Burkholderiales. To date, only a few studies have reported on the epidemiology, clinical symptoms, antibiotic susceptibility profiles, treatment and outcomes of Herbaspirillum huttiense -related infections in pediatric patients., Methods: The aim of this study was to present 3 years of H.huntiense data, antibiotic susceptibility profiles, systemic antibiotics and antibiotic lock therapy (ALT) options and clinical outcomes., Results: Fourteen episodes of infection in 12 patients were included in this retrospective study. The patients had a male/female ratio of 1:1 and a median age of 160.5 months (range, 3-198 months). Catheter-related bloodstream infection (CRBSI) was detected in 11 patients. Only 1 patient developed catheter-related infective endocarditis. The patient's catheter was removed, and she was successfully treated with systemic antibiotics for 4 weeks. Systemic antibiotics were used in all infections related to H. huttiense . In septic, critically ill patients, the catheter was removed, and systemic antibiotics were started. Port catheters were removed in 5 patients. ALT was performed in clinically stable patients. ALT using amikacin was administered to 6 patients through the port catheter. Two patients had a 2nd attack. After the 2nd ALT treatment, 1 patient cured, and the catheter of the other patient was removed due to persistent microbial growth in cultures. Antimicrobial susceptibility testing of the reported isolates showed susceptibility to meropenem (90%), ceftazidime (87%) and piperacillin/tazobactam (65%), with 92% resistance to colistin., Conclusion: H. huttiense is an emerging pathogen in CRBSI. Piperacillin/tazobactam, ceftazidime and meropenem appear to be good therapeutic options for the treatment of H. huttiense infections. ALT and systemic antibiotics can be used in H. huttiense -CRBSI to sterilize and preserve the central venous catheter., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The published experience concerning autologous peripheral blood stem cell collection in children is very limited., Methods: The data of pediatric patients who underwent autologous stem cell mobilization and apheresis between January 2011 and April 2020 were analyzed retrospectively., Results: We studied retrospectively 64 mobilization and apheresis procedures in 48 pediatric patients (34 males, 14 females), mean age of 7.31 ± 5.38 (range, 1.5-19.7) years, the underlying disease was mostly neuroblastoma (NBL). The body weight of 21 patients (43.75%) was 15 kg or less. The targeted autologous peripheral stem cell apheresis (APSCA) was successfully achieved in 98% of patients. Neuroblastoma patients were younger than the rest of the patients and underwent apheresis after receiving fewer chemotherapy cycles than others and all of them mobilized within the first session successfully. Plerixafor was added to mobilization in nine heavily pretreated patients (18.7%), median two doses (range, 1-4 doses). 11 patients (22.9%) underwent radiotherapy (RT) before mobilization with doses of median 24 Gy (range, 10.8-54.0 Gy). Patients with RT were older at the time of apheresis and had received more chemotherapy courses than patients without RT. As a result, patients with a history of RT had significantly lower peripheral CD34+ cells and CD34+ yields than those without RT. In 17 patients (35.4%), 22 different complications were noted. The most common complications were catheter-related infections (n:10, 20.8%), followed by catheter-related thrombosis in eight patients (16.7%)., Conclusions: Patients who had far less therapy before apheresis were more likely to mobilize successfully. Our study provides a detailed practice approach including complications during APSCA aiming to increase the success rates of apheresis in transplantation centers., (© 2024 Wiley Periodicals LLC.)

Background: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited., Objectives: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection., Method: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022., Results: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality., Conclusion: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD., (© 2024 Wiley Periodicals LLC.)

The purpose of this study was to evaluate the association between interleukin-33 (IL-33) and its receptor Soluble Suppression of Tumorigenicity-2 (sST2) levels and bacterial infections during febrile neutropenia (FN) in pediatric patients with acute lymphoblastic leukemia (ALL). In this prospective, case-control study, participants were divided into 3 groups: ALL patients with FN (Group A), ALL patients without neutropenia and fever (Group B), and healthy children without infection and chronic disease (Group C). There were 30 cases in each group. Blood samples for IL-33 and sST2 have been drawn from patients in Group A before the initiation of treatment and on days 1 and 5 of treatment, and from patients in Groups B and C at initiation. At admission, mean IL-33 level (39.02 ± 26.40 ng/L) in Group B and mean sST2 level (185.3 ± 371.49 ng/ml) in Group A were significantly higher than the other groups (p = 0.038, p < 0.001, respectively). No difference was observed in the mean IL-33 and sST2 levels in the 5-day follow-up of patients in Group A (p = 0.82, p = 0.86, respectively). IL-33 and sST2 levels were not associated with fever duration, neutropenia duration or length of hospitalization. While C-reactive protein (CRP) was significantly higher in patients with positive blood culture (p = 0.021), IL-33 (p = 0.49) and sST2 (p = 0.21) levels were not associated with culture positivity.  Conclusion: IL-33 and sST2 levels were not found valuable as diagnostic and prognostic markers to predict bacterial sepsis in patients with FN. What is Known: • Neutropenic patients are at high risk of serious bacterial and viral infections, but the admission symptom is often only fever. • Febrile neutropenia has a high mortality rate if not treated effectively. What is New: • Febrile neutropenia is not only caused by bacterial infections. Therefore, new biomarkers should be identified to prevent overuse of antibiotics. • Specific biomarkers are needed to diagnose bacterial sepsis in the early phase of febrile neutropenia., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We aimed to evaluate our pediatric HSCT recipients routinely monitored for adenoviremia and to determine the adequacy of this monitoring in predicting adenoviral disease (AD)., Methods: A retrospective cohort of patients who underwent allogeneic HSCT between January 2021 and August 2022, and routinely monitored for adenoviremia by real-time PCR was included in our survey. Demographic and clinical data of the patients were recorded. Incidence rates, risk factors, and mortality rates related to adenoviremia, and AD were analyzed., Results: Among 104 HSCTs performed in 94 patients adenovirus (AdV) was revealed in 27 (26%) episodes and adenoviremia in 18 (17.3%) HSCT episodes. AD without adenoviremia developed in nine episodes (8.6%). Disseminated disease was significantly more frequently detected in episodes with adenoviremia (p = .008). GVHD was independent risk factor for AdV detection (OR: 8.6, 95% CI: 2.03-33.7, p = .001). Viremia developed within a shorter time interval after HSCT in isolated episodes of adenoviremia compared to those with concomitant AD (p = .006). Initial and peak viral loads were significantly higher in adenoviremia with AD (p < .001). Mortality was higher in the AdV-detected episodes (p < .001) than in the AdV-undetected episodes. AdV-related mortality was found to be 22.2%. Adenoviremia increased the risk of mortality (OR: 1.2, 95% CI: 0.22-1.33, p = .01)., Conclusions: Adenoviremia monitoring is an important process in the detection of AD. Since some patients may develop AD without accompanying by adenoviremia, monitoring for AdV in blood samples should be supported with other monitoring methods in order to evaluate the probable involvement of different organs or systems., (© 2024 Wiley Periodicals LLC.)

Prophylaxis is the gold standard for the management of hemophilia A patients. It has been shown that prophylaxis regulated with pharmacokinetic (PK) data reduces frequency of bleeding and cost of treatment. To determine the best prophylaxis regimen, PK dosing tools using the Bayesian method have been developed. We aimed to compare two PK dosing tools. Blood samples were drawn before, 4, 24, and 48 h after FVIII infusions from patients with severe hemophilia A and inhibitor negative. FVIII levels were measured by PTT-based one-stage assay method. PK parameters obtained using WAPPS and myPKFiT, which are web-accessible PK dosing tools using Bayesian algorithm, and daily prophylaxis dose estimated by the programs were compared. Forty-two hemophilia A patients [median age 13 years (IQR 8.9-16.4)] included in the study. There was no difference between the daily dose of FVIII given for prophylaxis and the dose recommended by the myPKFiT for the 1% trough level; whereas, a significant difference was found with the WAPPS. The half-lives of FVIII did not differ between the two dosing tools; however, significant differences were found in the estimated dose, clearances, and times to 1% trough level. There was no significant difference between PK data of patients who received Advate® and those who received non-Advate® factor concentrates. Choice of PK dosing tool can affect recommended FVIII dose. However, target trough levels should be individualized according to bleeding phenotype and daily activity of patient., Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01671-0., Competing Interests: Conflict of interestNone declared., (© The Author(s), under exclusive licence to Indian Society of Hematology and Blood Transfusion 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objectives: To evaluate the effectiveness of national iron prophylaxis policy in 9-12 mo-old infants in Turkey., Methods: This study was planned as a cross-sectional study, and it included healthy infants aged 9 to 12 mo who presented to the pediatric outpatient clinic for routine check-ups. Parents were interviewed to identify risk factors for iron deficiency (ID) and gather information on Fe +3  - iron polymaltose complex (IPC) prophylaxis usage. Blood samples were collected for hemogram and ferritin analysis. Multiple logistic regression analyses were conducted to determine risk factors for ID and iron deficiency anemia (IDA)., Results: The study included 317 infants. In the non-prophylaxis group, the frequency of IDA was 31.1%, compared to 13.4% in the regular prophylaxis group. Iron deficiency was detected in 25% of individuals receiving regular prophylaxis and 13.1% of those without prophylaxis. The risk factors for IDA were insufficient iron diets (OR 2.45, 95% CI: 1.35-4.45) and not receiving Fe +3 - IPC prophylaxis (OR 2.57, 95% CI: 1.24-5.31). The relationship between Fe +3  - IPC prophylaxis and ID did not reach statistical significance (p = 0.253)., Conclusions: Fe +3  - IPC prophylaxis is associated with a lower risk of iron deficiency anemia, but not iron deficiency., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Purpose: It was aimed to evaluate the retinochoroidal microvascular alterations of pediatric beta-thalassemia patients and investigate the effect of blood transfusion on perfusion among transfusion-dependent thalassemia (TDT), by means of optical coherence tomography angiography (OCTA)., Methods: In this multicentered, prospective, cross-sectional study, 56 TDT, 14 non-TDT (NTDT), and 63 healthy children were evaluated. The vessel density (VD) in superficial capillary plexus (SCP), deep capillary plexus, radial peripapillary capillary network, choriocapillaris, and the foveal avascular zone area (FAZ) were evaluated by OCTA. Before and after transfusion values ​​of the TDT group were compared, and correlations were made with blood values ​​and iron accumulation., Results: Foveal and parafoveal zones were significantly thinner among TDT patients, with larger FAZ area. Macula VD of SCP and ppVD was lowest in NTDT group. In the TDT group, a decrease in retinal nerve fiber thickness and ppVD values was detected ​​after transfusion. A negative significant relationship was found between both hemoglobin (Hb), hematocrit (Htc), and ppVD., Conclusions: OCTA provides a better insight into retinal and choriocapillaris vascular impairment influenced by tissue hypoxia and oxidative stress in different clinical phenotypes of beta-thalassemia., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: Beta thalassemia major is an inherited hemoglobin disorder resulting in chronic hemolytic anemia. Cardiac involvement is the main cause of death in patients. Speckle-tracking echocardiography is a feasible method for the evaluation of cardiac function via an assessment of the longitudinal deformation of the myocardium through the cardiac cycle. The aim of our study is to evaluate the association between vitamin D deficiency and deformation of the left ventricular myocardium measured by speckle-tracking echocardiography in children with thalassemia major., Methods: In this prospective study, 33 thalassemic patients with vitamin D deficiency were enrolled. Cardiac magnetic resonance T2* value, conventional echocardiography, and speckle tracking, and also left ventricular longitudinal and circumferential strain values were measured. Myocardial functions of the patients with vitamin D deficiency or insufficiency were evaluated by speckle-tracking echocardiography before and after vitamin D replacement., Results: The mean age of the patients was 15.4 ± 3.09 years. Vitamin D level was deficient in 30 (90%) and insufficient in 3 (10%) of them. Speckle-tracking analysis showed a significantly decreased absolute value of the left ventricular global longitudinal strain before vitamin D replacement. A significant improvement in the global longitudinal strain was detected after vitamin D replacement (P < 0.05). A statistically significant increase was observed in parameters showing left ventricular systolic and diastolic functions after vitamin D replacement., Conclusion: Vitamin D deficiency is frequently observed and causes decreased contractility in thalassemic patients. In our study, we observed that our patients' cardiac functions had improved after vitamin D replacement therapy.

Objective: Patients with inherited bleeding disorders faced problems in accessing healthcare during coronavirus disease 2019 pandemic. This study aimed to investigate the health problems of patients with inherited bleeding disorders during the coronavirus disease 2019 pandemic., Material and Methods: Children and adult patients with inherited bleeding disorders who had a coronavirus disease 2019 infection between March 2020 and November 2021 were retrospec- tively evaluated., Results: Seven hundred seventy-two patients were reviewed, and 65 patients who had a coro- navirus disease 2019 infection (Male/Female: 58/7, mean age 28.2 ±14.1 years) were analyzed. Sixty patients (92%) had hemophilia A or B or von Willebrand's disease and 5 (8%) had rare bleeding disorders. Sixteen (24.6%) patients had a comorbid disease and 6 (9.2%) needed hospitalization due to severe coronavirus disease 2019 infection. Seven patients (10.7%) expe- rienced a bleeding episode and were treated with factor concentrates. Totally, 64 (98.46%) patients recovered from the coronavirus disease 2019 infection and 1 died., Conclusion: Patients with inherited bleeding disorders and coronavirus disease 2019 infection mostly had a mild/moderate course of the disease.

Background: Patients with thalassemia need regular blood transfusions to maintain normal growth and suppression of ineffective erythropoiesis. Packed red blood cell (RBC) units can be delivered by infusion pumps (IPs); however, IPs may cause mechanical stress-induced RBC lysis. This study aimed to investigate the biomarkers of hemolysis related to transfusion techniques in patients with thalassemia., Material and Methods: Eighty-one thalassemia patients compared to those 42 healthy controls in terms of hemolysis markers (hemoglobin, plasma free hemoglobin (Hb), haptoglobin, potassium (K), lactate dehydrogenase (LDH)) before transfusion. Considering the age and peripheral venous diameter of the patient, the physician decided on the caliber of vascular access device (22 G or 24 G) for transfusion and the method to be used (gravitational method [GM] or IP). Hemolysis markers were repeated after transfusion in thalassemia patients., Results: Packed RBC units were transfused to 24 (30 %) patients by IP and 57 (70 %) patients by GM. Plasma free Hb was significantly increased from 4.76 ± 7.92 mg/dL to 9.01 ± 7.66 mg/dL following transfusion (p < 0.001). There was no significant difference between IP and GM in terms of plasma free Hb increase. Post-transfusion plasma free Hb, LDH, and K levels significantly increased in patients who were transfused with 24 G catheters compared to those transfused with 22 G., Conclusion: An elevation in LDH levels was detected after transfusion with volumetric IPs; however, plasma free Hb or K levels were not affected by the transfusion method. Studies are needed to determine the factors associated with hemolysis after transfusion., Competing Interests: Conflicts of interest None declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

To evaluate the general characteristics of pediatric Behçet's disease (BD) patients with thrombus and to present the clinical features, treatment responses and prognosis of patients with intracardiac thrombus. The clinical characteristics and outcomes of 15 patients with thrombus among 85 pediatric BD patients followed in the Department of Pediatric Rheumatology were evaluated retrospectively. Of the 15 BD patients with thrombus, 12 (80%) were male, 3 (20%) were female. The mean age at diagnosis was 12.9 ± 1.1 years. Thrombus was present at the time of diagnosis in 12 patients (80%), while thrombus developed in three patients within the first three months after diagnosis. The most common site of thrombus was the central nervous system (n = 9, 60%), followed by deep vein thrombus (n = 6, 40%) and pulmonary artery thrombus (n = 4, 26.6%). Three male patients (20%) developed intracardiac thrombus. The overall intracardiac thrombus rate in the 85 patients was 3.5%. Two of the three patients had thrombus in the right, and one had thrombus in the left heart cavity. In addition to steroids, 2 of the 3 patients received cyclophosphamide, while the patient with thrombus localized in the left heart cavity was given infliximab. In the follow-up, the two patients with thrombus in the right heart cavity were switched to infliximab because of resistance to cyclophosphamide. Complete resolution was observed in 2 of the 3 patients on infliximab; a significant reduction in the thrombus of the other patient was achieved. Intracardiac thrombus is a rare presentation of cardiac involvement in BD. It is usually observed in males and in the right heart. Although steroids and immunosuppressive agents such as cyclophosphamide are recommended as first-line treatment, favorable outcomes can be achieved with anti-TNFs in resistant cases., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The aim of this study is to develop new perspectives to prevent or reduce potential organ damage due to iron-mediated oxidation in thalassemia major patients., Methods: Seventy patients were included in this study. Blood samples were taken from the patients before and after transfusion. Total thiol, native thiol, disulfide, disulfide/native thiol percentage ratio, ischemia modified albumin (IMA), total antioxidant status (TAS), total oxidant status (TOS), and ferroxidase levels were determined. Additionally, undepleted thiol level (UTL) was determined as a new parameter associated with organ damage., Results: After transfusion, the levels of native thiol, total thiol, disulfide, TAS, ferroxidase, and TOS were higher, while the IMA levels and disulfide/native thiol percent ratio were lower. Significant correlations were found between antioxidant and oxidant tests before and after transfusion. Additionally, a negative correlation was found between the TOS and UTL levels of the patients measured before the transfusion., Conclusion: In the present study, transfusion therapy increased both oxidation and the antioxidant levels. In addition, the term UTL has been introduced as a parameter that enables the determination of the oxidation level that may cause potential organ damage in transfusion-dependent thalassemia patients.

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., (© 2022 John Wiley & Sons Ltd.)

During CD34 + stem cell count to determine the number of stem cells in the allografts from pediatric donors, we noticed a considerable amount of early hematogones (eHGs) within the stem cell gate in flow cytometry. Since the number of hematogones causes a decrease in the total number of stem cells counted within the graft, we planned a retrospective study to analyze the effect of eHGs on transplant outcomes. We also wanted to show how allografts containing high amounts of early HGs affect transplant outcomes. Quantification of CD34 numbers and the number of eHGs were determined by flow cytometry. Patients were divided into 2 groups according to the number of CD 34 + cells calculated after subtracting the number of hematogones within the allograft. Those who received < 2 × 10 6 /kg CD34 + cells and ≥ 2 × 10 6 /kg were defined as group 1 and 2, respectively. Twenty-six patients and their 26 donors were included in the study. The median age of patients was 6.5 years and 5.4 years in Group 1 and 2, respectively. The median donor age was 9 years in Group 1 and 7 years in Group 2. The ages and genders were similar in the two groups ( p  > 0.05). The number of nucleated cells given to both groups was not different. The number of early hematogones given to both groups was similar ( p  = 0.93). The mean times to myeloid and platelet engraftments were also similar in the two groups. In this study, we provided trilineage engraftment to all patients in two groups. We could not find a considerable effect of these eHGs in myeloid and platelet engraftments. However, the number of patients included in our study is low, therefore we suggest a study including a large number of donors in order to confirm our findings., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Indian Society of Hematology and Blood Transfusion 2022.)

Purpose: Hemophilia is a hereditary coagulation disorder characterized by acute hemorrhages into the musculoskeletal system, leading eventually to arthropathy and disability. Chronic inflammation of the synovial membrane arises as a result of frequent joint hemorrhage. Proteolytic enzymes in the blood and cartilage cause deterioration after that, and joint space narrows. Chronic hemophilic arthropathy develops as a result of these unfavorable developments, which occur more quickly, especially in the target joints. Balance is a process that allows us to maintain our orientation in three-dimensional space while also regulating our body posture to avoid falling. After the central nervous system evaluates deep stimuli from sensory, visual, and auditory receptors, movement of the corresponding muscle groups is delivered., Methods: The goal of this study was to investigate how impairment to deep sensory receptors (proprioception) in the arthropathic joint structure affected hemophiliacs' balance. The study comprised 34 patients with hemophilic arthropathy, and 34 age and weight matched healthy volunteers., Results: When balance tests of patients with hemophilic arthropathy were compared to healthy controls, hemophiliacs had a greater risk of falling. As the degree of arthropathy increased, so did the risk of falling and balance test values in individuals with hemophilic arthropathy., Conclusions: Treatment and coagulation factor prophylaxis to prevent the onset of arthropathy will improve patients' quality of life and reduce morbidity associated with frequent falls and bleeding., Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01526-0., Competing Interests: Competing InterestThe authors have no relevant financial or non-financial interests to disclose.Conflict of Interest and Source of FundingNone declared., (© The Author(s), under exclusive licence to Indian Society of Hematology and Blood Transfusion 2022.)

Objective: Anthracyclines are widely used in the treatment of acute lymphoblastic leukemia (ALL). However, cardiotoxicity is the most critical side effect that requires dose limitation. It is thought to occur at first exposure, but the clinical presentation may occur years later. In this study, we aimed to determine the time of initial damage and cardiotoxicity that develops in children with ALL., Methods: In this prospective study, 13 patients with newly diagnosed intermediate-risk precursor B cell ALL treated with the ALL-IC BFM 2009 protocol were included. Conventional echocardiography, tissue Doppler imaging (TDI), and speckle-tracking echocardiography (STE) were performed in all the patients before chemotherapy, after completing the induction phase, and at the end of the reinduction phase., Results: The mean age of the patients was 7.8±4.6 (3.1-16.3) years. Myocardial velocity during systole (Sm) determined by TDI at the interventricular septum significantly decreased during the induction phase. Despite a decrease in STE parameters, a statistically significant reduction was determined in the global longitudinal strain rate at both left and right ventricles at the end of the induction. Nevertheless, a statistically significant increase was observed among the conventional echocardiographic findings in the left ventricular end-diastolic diameter at the end of the reinduction., Conclusion: During the treatment of ALL, subclinical anthracycline-associated cardiotoxicity develops in the early stages of treatment. The findings detected by TDI and STE could be missed by conventional echocardiography. We recommend evaluating patients with these newly developed techniques to detect subclinical cardiotoxicity at an early stage and starting appropriate therapy on time.

Objectives: We aimed to evaluate the impact of pretreatment folate and vitamin B 12 deficiencies on the frequency of complications and peripheral blood recovery, in children with acute lymphoblastic leukemia (ALL)., Methods: Pre-induction serum folate and vitamin B 12 levels of 88 newly diagnosed ALL patients were evaluated retrospectively. Folate < 3 ng/mL and vitamin B 12 < 200 pg/mL were accepted as deficiency. Median hemoglobin, absolute neutrophil count (ANC), and platelet counts, transfusion needs, and complications such as mucositis, febrile neutropenia (FN), bleeding at diagnosis, at 15th and 33rd day of induction, were assessed. Recovery of peripheral blood count, which was defined as an ANC > 1.0 × 10 9 /L and platelet count > 100 × 10 9 /L at 33rd day of chemotherapy were also evaluated., Results: Folate or vitamin B 12 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 B 12 -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., Conclusion: Although pre-induction low serum levels of vitamin B 12 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.

Background: Febrile neutropenia (FN) is a common and serious complication in patients with leukemia. Hemostasis and inflammation are two interrelated systems in response to infection. We aimed to investigate the course of thrombin formation in febrile neutropenia attack of children with acute lymphoblastic leukemia (ALL)., Methods: Thrombin generation was monitored in children treated for ALL at diagnosis of febrile neutropenia (FN) (t < sub > 0 < /sub > ), at 48 < sup > th < /sup > hour of FN (t1) and after recovery from neutropenia (t < sub > 2 < /sub > )., Results: Twenty-nine patients and 50 healthy children as control were enrolled into the study. Mean endogenous thrombin potential (ETP) and mean peak value of thrombin results at t < sub > 1 < /sub > were significantly higher than at t < sub > 0 < /sub > , t < sub > 2 < /sub > and control groups, respectively. A positive but statistically nonsignificant correlation between ETP values at t < sub > 1 < /sub > and duration of neutropenia was observed., Conclusion: Although thrombin generation is enhanced both due to chemotherapy or malignancy itself, our results revealed that thrombin formation also increased in neutropenic infection of children with leukemia.

Background: Autoimmune atrophic gastritis (AIG) is very rare in children. Despite a better understanding of histopathologic changes and serological markers in this disease, underlying etiopathogenic mechanisms and the effect of Helicobacter pylori (H pylori) infection are not well known. We aimed to investigate the relation between AIG and H pylori infection in children., Materials and Methods: We evaluated the presence of AIG and H pylori infection in fifty-three patients with positive antiparietal cell antibody (APCA). Demographic data, clinical symptoms, laboratory and endoscopic findings, histopathology, and presence of H pylori were recorded., Results: The children were aged between 5 and 18 years, and 28 (52.8%) of them were male. Mean age was 14.7 ± 2.6 years (median: 15.3; min-max: 5.2-18), and 10 (18.8%) of them had AIG confirmed by histopathology. In the AIG group, the duration of vitamin B12 deficiency was longer (P = .022), hemoglobin levels were lower (P = .018), and APCA (P = .039) and gastrin (P = .002) levels were higher than those in the non-AIG group. Endoscopic findings were similar between the two groups. Intestinal metaplasia was higher (P = .018) in the AIG group. None of the patients in the AIG group had H pylori infection (P = .004). One patient in the AIG group had enterochromaffin-like cell hyperplasia., Conclusions: Our results show that, in children, H pylori infection may not play a role in AIG. AIG could be associated with vitamin B12 deficiency, iron deficiency, and APCA positivity in children. APCA and gastrin levels should be investigated for the early diagnosis of AIG and intestinal metaplasia., (© 2020 John Wiley & Sons Ltd.)

Objective: Immune thrombocytopenia (ITP) is a rare autoimmune disease and hematologic disorder characterized by reduced platelet counts that can result in significant symptoms, such as bleeding, bruising, epistaxis, or petechiae. The thrombopoietin receptor agonist eltrombopag (EPAG) is a second-line agent used to treat chronic ITP purpura in adults and children., Materials and Methods: The present retrospective study evaluated the efficacy, safety, and side effects of EPAG treatment in pediatric patients with acute refractory and chronic immune thrombocytopenia, particularly focusing on iron-deficiency anemia., Results: The diagnosis was chronic ITP in 89 patients and acute refractory ITP in 16 patients. The mean age of patients was 9.5±4.5 years (minimum-maximum: 1.2-18 years) at the beginning of EPAG treatment. The overall response rate was 74.3% (n=78). The mean time for platelet count of ≥50x109/L was 11.6±8 weeks (range: 1-34 weeks). The treatment was stopped for 27 patients (25.7%) at an average of 6.8±9 months (range: 1-38 months). The reason for discontinuation was lack of response in 18 patients, nonadherence in 4 patients, and hepatotoxicity in 2 patients. Response to treatment continued for an average of 4 months after cessation of EPAG in 3 patients., Conclusion: Results of the current study imply that EPAG is an effective therapeutic option in pediatric patients with acute refractory and chronic ITP. However, patients must be closely monitored for response and side effects during treatment, and especially for iron deficiency.

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.

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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.)

Biallelic variants in the ERCC excision repair 6 like 2 gene ( ERCC6L2 ) are known to cause bone marrow failure (BMF) due to defects in DNA repair and mitochondrial function. Here, we report on eight cases of BMF from five families harboring biallelic variants in ERCC6L2 , two of whom present with myelodysplasia. We confirm that ERCC6L2 patients' lymphoblastoid cell lines (LCLs) are hypersensitive to DNA-damaging agents that specifically activate the transcription coupled nucleotide excision repair (TCNER) pathway. Interestingly, patients' LCLs are also hypersensitive to transcription inhibitors that interfere with RNA polymerase II (RNA Pol II) and display an abnormal delay in transcription recovery. Using affinity-based mass spectrometry we found that ERCC6L2 interacts with DNA-dependent protein kinase (DNA-PK), a regulatory component of the RNA Pol II transcription complex. Chromatin immunoprecipitation PCR studies revealed ERCC6L2 occupancy on gene bodies along with RNA Pol II and DNA-PK. Patients' LCLs fail to terminate transcript elongation accurately upon DNA damage and display a significant increase in nuclear DNA-RNA hybrids (R loops). Collectively, we conclude that ERCC6L2 is involved in regulating RNA Pol II-mediated transcription via its interaction with DNA-PK to resolve R loops and minimize transcription-associated genome instability. The inherited BMF syndrome caused by biallelic variants in ERCC6L2 can be considered as a primary transcription deficiency rather than a DNA repair defect., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Background and Objectives: Acute promyelocytic leukemia (APL), is a distinct subtype of acute myeloid leukemia (AML) characterized by a tendency to hemorrhage and excellent response to all-trans retinoic acid (ATRA). In this retrospective study, we aimed to determine the incidence, clinical symptoms, toxicities, and outcome of children with APL in our center., Methods: We retrospectively reviewed the medical records of children (age < 18 years) diagnosed with APL in our pediatric hematology department between January 2006-December 2016., Results: Pediatric APL represents 20.5% of AML cases in this cohort. Most of the cases presented as classical M3, albeit hypogranular variant was described in 12% of the cohort. Patients with hypogranular variant APL were differed from classical APL by co-expression of CD2 and CD34. About ¾ of APL patients had hemorrhagic findings at admission or the induction treatment. Severe bleeding manifested as intracranial hemorrhage was present in three patients and intracranial arterial thrombosis was present in one. Six patients showed side effects of ATRA such as pseudotumor cerebri, differentiation syndrome resulting in dilated cardiomyopathy, and pulmonary infiltrates. Five-year overall survival (OS) and early death rate were found to be 82.5% and 12% respectively., Conclusions: A high frequency (20.5%) of APL was noted among children with AML in this single-center study. The overall mortality rate was 17.5%. Since the induction death rate was 12% and life-threatening bleeding was the primary problem, awareness and urgent treatment are critical factors to reduce early losses., Competing Interests: Competing interests: The authors have declared that no competing interests exist.

Objective: This study aimed to define the status of juvenile myelomonocytic leukemia (JMML) patients in Turkey in terms of time of diagnosis, clinical characteristics, mutational studies, clinical course, and treatment strategies., Materials and Methods: Data including clinical and laboratory characteristics and treatment strategies of JMML patients were collected retrospectively from pediatric hematology-oncology centers in Turkey., Results: Sixty-five children with JMML diagnosed between 2002 and 2016 in 18 institutions throughout Turkey were enrolled in the study. The median age at diagnosis was 17 months (min-max: 2-117 months). Splenomegaly was present in 92% of patients at the time of diagnosis. The median white blood cell, monocyte, and platelet counts were 32.9x109/L, 5.4x109/L, and 58.3x109/L, respectively. Monosomy 7 was present in 18% of patients. JMML mutational analysis was performed in 32 of 65 patients (49%) and PTPN11 was the most common mutation. Hematopoietic stem cell transplantation (HSCT) could only be performed in 28 patients (44%), the majority being after the year 2012. The most frequent reason for not performing HSCT was the inability to find a suitable donor. The median time from diagnosis to HSCT was 9 months (min-max: 2-63 months). The 5-year cumulative survival rate was 33% and median estimated survival time was 30±17.4 months (95% CI: 0-64.1) for all patients. Survival time was significantly better in the HSCT group (log-rank p=0.019). Older age at diagnosis (>2 years), platelet count of less than 40x109/L, and PTPN11 mutation were the factors significantly associated with shorter survival time., Conclusion: Although there has recently been improvement in terms of definitive diagnosis and HSCT in JMML patients, the overall results are not satisfactory and it is necessary to put more effort into this issue in Turkey.

In order to decrease donors' exposure to granulocyte-colony stimulating factor (G-CSF), we compared the effect of two versus three days of G-CSF priming on CD34+ yield in bone marrow (BM) harvest. Although the number of BM-CD34+ cells was higher in 3day G-CSF priming, we achieved the same number of CD34+ cells per recipient's weight in 2day G-CSF priming group, too. In addition, the number of total nucleated cells (TNC) harvested from BM were similar with two or three day regimen. But mononuclear cells (MNC) of the BM graft was higher in the 3day G-CSF priming group. Similar to CD34+ cell numbers, BM harvest yielded similar TNC, and MNC numbers per kilogram of the recipient. We also found that, young donors (≤10year) had more peripheral blood MNC, bone marrow MNC and CD34+ cell numbers. Another interesting finding of this study was obtaining adequate number of peripheral blood stem cells for leukapheresis with three day G-CSF administration. Since engrafment times were also similar in two groups, we concluded that 2-days G-CSF priming was resulted in sufficient mobilization of BM stem cells., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

PH is a rare condition with high mortality rate after pediatric HSCT. As clinical presentation is non-specific and may mimic other conditions, a high degree of suspicion is required for diagnosis. Here, we present a patient with stage-IV neuroblastoma who developed PAH after autologous HSCT. After exclusion of other causes of PH, we regarded that this condition was secondary to HSCT., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Invasive fungal infections have turned out to be a significant cause of morbidity and mortality in pediatric patients with malignant disorders. Massive hemoptysis, a rare complication of invasive pulmonary aspergillosis, may threaten the lives of patients, usually during the resolution of neutropenia. In this report, we describe a patient with massive hemoptysis due to invasive pulmonary aspergillosis whose bleeding was controlled successfully with off-label use of recombinant factor VIIa and subsequent coil embolization of the right pulmonary artery.