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Allogeneic hematopoietic stem cell transplantation stands as a promising cure for a variety of diseases. However, the potential of acute or chronic graft-versus-host disease (GvHD), which leads to significant morbidity and mortality, remains a cause for concern. GvHD occurs due to the complex interactions of immune cells from the graft and the host cells. Despite the existence of prophylactic treatments, GvHD may still occur, and the resistance to conventional therapies necessitates novel approaches and treatments. Mesenchymal stem cells, which are pluripotent stem cells capable of self-renewal and multilineage differentiation, have gained attention for their low immunogenicity and ability to be sourced from various origins. They have shown promise as therapeutic tools for the cell-based treatment of inflammatory, immune-mediated, and degenerative diseases owing to their remarkable abilities in immunomodulation, immunosuppression, and tissue regeneration. In GvHD, MSCs have demonstrated therapeutic potential through paracrine activity and organelle transfer via nanotubes, microvesicles, or exosomes. The emergence of MSCs as a treatment for severe steroid-resistant GvHD gained attention in the early 2000s. While initial studies have demonstrated encouraging results in the use of MSCs for the prevention of GvHD, there is still a need for further investigation. Therefore, in this current review, we aim to delve deeper into MSC's features and their clinical applications in the case of GvHD treatment. [ABSTRACT FROM AUTHOR]

Objective: Hematopoietic stem cell transplantation is recommended as a first-line treatment in a pediatric severe aplastic anemia, if the patient has an HLA-matched family donor. In this study, we aimed to evaluate the allogeneic hematopoietic stem cell transplantation outcomes of our patients who were followed with a diagnosis of aplastic anemia. Material and Methods: From April 2010 to July 2017, 10 pediatric acquired aplastic anemia patients treated with allogeneic hematopoietic stem cell transplantation at our center were evaluated retrospectively from patient charts and computer records. Results: A total of 12 allogeneic stem cell transplantations had been performed in 10 patients with severe and very severe acquired aplastic anemia. Mean age during transplantation was 10.9±3.76 (min=4.6-max=16.1) years and 80% of the patients were female. Mean interval from diagnosis to transplantation was 10.1±7.65 (min=3-max=31) months and all of the donors were siblings. The mean nucleated cell count was 4.69±2.17x108 (min=1.13x108-max=8.43x108) and CD34+ cell count was 3.25±1.39x106 (min=1.65x106-max=6.55x106). Mean neutrophil engraftment time was 16.2±0.8 (min=15-max=17) days and platelet engraftment time was 26±6.5 (min=16-max=37) days. Acute graft versus host disease was not observed in any patient and limited chronic pulmonary graft versus host disease was seen in only one patient. Primary graft failure developed in one patient and secondary graft failure in another patient. None of the patients developed myelodysplastic syndrome (MDS), leukemia, paroxysmal nocturnal hemoglobinuria (PNH) or secondary malignancy during follow-up. One patient died due to intracranial hemorrhage on day +16 after transplantation. Mixed chimerism was present in 66.7% and all patients are now followed up with complete hematological remission. Conclusion: We achieved 90% overall survival in our patients over a 7-year follow-up period. Considering the high rates of relapse and clonal hematopoiesis after immünosuppressive treatment in studies reported in the literature, we believe that allogeneic hematopoietic stem cell transplantation can be used as a first-line treatment in children with aplastic anemia, especially if there is an HLA-compatible family donor. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Upper extremity deep vein thrombosis (UEDVT) is extremely rare in children and adolescents. Paget - Schroetter Syndrome (PSS) is the primary, spontaneous thrombosis of the subclavian venous (SV) axillary tract. Herein, we report on PSS in two children who did regular body building exercises. 16-year-old two male patients admitted with complaints of swelling, coldness and pain on the right upper extremity. Their recent history disclosed that they have been doing advanced body building exercises for the last year. Physical examination revealed a difference of 4 cm and 5 cm in the diameter of each arm, as well as coldness and venous engourgement in the upper extremities. An acute thrombus was present in the proximal right SV lumen and no flow was detected on upper extremity venous doppler ultrasaund. Surgical treatment was performed in addition to medical thrombosis treatment. Early diagnosis and treatment of PSS is important for better outcomes. PSS should be considered in young patients with UEDVT, especially those with a history of vigorious exercise. [ABSTRACT FROM AUTHOR]

Infections are a significant cause of morbidity and mortality of chemotherapy-induced neutropenia in children with acute leukemia. The aim of this study was to evaluate microbiologically documented infections (MDIs) during febrile neutropenia (FN) episodes and their relation to mortality. Four hundred eighty-seven FN episodes of 140 children were enrolled in this single-center study, and MDI in those FN episodes was retrospectively examined. Eighty-four patients (60%) had at least one positive peripheral blood, central line, or urine culture. MDIs were detected in 163 of 487 (33.4%) FN episodes of 84 children with leukemia. Gram-negative bacteria, Gram-positive bacteria, and fungal agents were isolated in 52.7%, 40.4%, and 6.9% of whole episodes. Coagulase-negative Staphylococci and Enterococci were the most detected Gram-positive bacteria. Klebsiella spp. and Escherichia coli were the most common Gram-negative bacteria isolated in the entire cohort. A central line was present in 145 MDI episodes, and catheter removal was required in 35 cases (17.7%) due to infection with Gram-negative bacteria, Gram-positive bacteria 43%, 28.5%, and fungus 28.5%, respectively. MDI-related mortality was 9.8%. The highest mortality rate (16.7%) was observed in Gram-negative bacteria and patients with relapsed and resistant leukemia. The most common infectious agent related to mortality was Klebsiella (31%). Resistance to third-or fourth-generation cephalosporins in Gram-negative bacteria was found to be over 50% of our cohort uri. Empirical antibiotic therapy at the onset of FN in neutropenic patients is crucial; therefore, the institution's predominant pathogens and resistance patterns should guide the choice of empirical antimicrobials. To reduce mortality and morbidity, each center should know its local epidemiological data and antibiotic susceptibility. [ABSTRACT FROM AUTHOR]

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 retrospectively evaluated. Results: Seven hundred seventy-two patients were reviewed, and 65 patients who had a coronavirus 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%) experienced 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Cancer care is progressively became as a significant worldwide challenge. Wars can cause destructions and delays in cancer diagnosis and treatment of displaced people. Cancer cure rates need to be improved in indefensible populations such as refugees. In this study, we purposed to highlight the clinical peculiarities and outcomes of refugee children with cancer in our hospital. Our purpose was to present our findings and contribute to improve the health care for these children. Seventy one refugee pediatric patients admitted to the oncology and hematology units of our hospital between April 2011 and January 2019 were included in this study. The demographic characteristics of the patients at the initial diagnosis, their countries of origin, living conditions, histopathological diagnoses, treatments, relapse, and mortality data were analyzed retrospectively from the patient files. The median age of patients was 6.5±4.5 years, and the male-to-female ratio was 39/32. While 44 patients (61.9%) presented with complaints and had primary diagnoses in our hospital, the remaining 27 patients (38.1%) were diagnosed in their country and applied to our hospital for treatment. Our mean follow-up period was 18.2±18.8 months (1-90 months). As a result, 44 patients (62%) were alive and 22 (31%) were dead. The survival rate without relapse in the second year was 83.6%. Two and fiveyear survival rates were 77.5% vs. 58.1% respectively. Compared to Turkish children, lower survival rates were found in refugee children. In addition to cancer-specific factors such as tumor type and stage, some problems such as shelter, communication, adherence to treatment, and difficulties supplying medicine may be responsible for lower survival rates in refugee children. Further studies are needed to improve the survival rates of patients. [ABSTRACT FROM AUTHOR]

Objective: The role of combination regimens in the treatment of invasive fungal infections (IFIs) in hematologic malignancies remains unclear. We aimed to demonstrate data about combined antifungal therapy (CAT) in pediatric leukemia patients with IFI. Method: Between January 2014 and December 2018, a total of 33 IFI episodes in 28 leukemia patients were analyzed retrospectively. Results: The study patients had acute lymphoblastic leukemia (n=19), acute myeloblastic leukemia (n=9), leukemia relapse (n=21; 75%) and remission (n=7; 25%). The patients were classified as having possible (n=26; 78.8%), probable (n=5; 15.1%) and proven IFI (n=2; 6.1%). Liposomal amphotericin B (LamB) was the most preferred agent (50%) in monotherapy. Mean duration of monotherapy was 12.84±4.28 (5-24) days. LamB plus voriconazole (54.5%) was the most commonly preferred CAT. Mean duration of CAT was 42.36±36.4 days, and this combination regimen was not changed throughout the treatment period (p=0.571). Total and IFI-related mortality rates were 60.7% vs 46.4%, respectively. Mortality rates were significantly higher in patients with relapse (p=0.006). Complete response was obtained in 81.8% of surviving patients. Side effects of CAT were observed at quite a low level. Conclusion: CAT has been found to be safe in the treatment of IFI episodes of pediatric leukemia. Uncontrolled underlying disease is the most important factor affecting the mortality rates in IFI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Pneumatosis cystoides intestinalis (PCI) is a disorder in which widespread air sacs are present in mucosa, submucosa, subserosa, and intraabdominal area of the intestinal wall. It has a heterogeneous clinical presentation as a rare complication of intestinal graft‐versus‐host disease (GVHD). Computed tomography is the preferred imaging method for the diagnosis. Since the air sacs could be ruptured spontaneously, the presence of free air in the peritoneal cavity does not confirm intestinal perforation. The conservative treatment approach is sufficient in cases that do not require urgent surgical intervention, such as perforation or obstruction. Case: Here, we present a 2.5‐year‐old patient diagnosed with primary hemophagocytic lymphohistiocytosis (pHLH), who underwent allogeneic hematopoietic stem cell transplantation from a matched unrelated donor (MUD) and developed PCI secondary to intestinal GVHD 14th months after HSCT. Conclusions: Pneumatosis cystoides intestinalis, which is a rare complication, should be kept in mind, especially in patients with intestinal GVHD and receiving intensive immunosuppressive, octreotide, and steroid treatment after HSCT. [ABSTRACT FROM AUTHOR]

Objectives: 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). Methods: Pre-induction serum folate and vitamin B12 levels of 88 newly diagnosed ALL patients were evaluated retrospectively. Folate < 3 ng/mL and vitamin B12 < 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 × 109/L and platelet count > 100 × 109/L at 33rd day of chemotherapy were also evaluated. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Factor VIII (FVIII) prophylaxis is now considered a gold standard for the treatment of hemophilia A patients to prevent bleeding and maintain musculoskeletal function. FVIII prophylaxis, tailored with pharmacokinetic data, is the most successful approach in preventing bleeding and reducing the cost of treatment. Material and Methods: In this study, 17 patients with severe hemophilia A (median age 11.5 years, median factor 25 U/kg) whose FVIII pharmacokinetic data were obtained through the myPKFiT web access program, were presented. Results: The mean FVIII half-life of the patients was 9.1 hours (min-max: 6.8-11.4); the mean FVIII clearance was 4.7 ml/hour/kg (min-max: 2.6-6.8); and the mean duration of FVIII levels under 1% was 47 hours (min-max: 33-61). The half-life of FVIII was increased with the age of the patient. When a weekly dose schedule simulated with the target FVIII trough level above 1%, it was observed that the dose of FVIII was sufficient in three, it was high in five, and it was insufficient in nine patients. Conclusion: In our study, prophylaxis doses and frequencies were adjusted according to the FVIII pharmacokinetic data. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The use of therapeutic plasma exchange (TPE) in pediatric intensive care units (PICUs) has increased in recent years. In this study, we retrospectively report and discuss therapeutic plasmapheresis management in the intensive care unit of a children's hospital. Material and Methods: Demographic, clinical and laboratory data of the patients who were subjected to TPE between 1 January 2016 and 1 June 2018 were obtained from the hospital information system and medical records. Results: A total of 190 sessions of therapeutic plasma exchange was performed on 43 patients (Male:Female ratio of 1:1.26). The median age of the patients was 99 months (range 6-214 months). The most common indication was sepsis-related multiple organ failure (n:23, 53.5%). All procedures were conducted using the cell-separator centrifugal method. The ratio of complications during manipulations was 5.7%. No life-threatening complication associated with the therapeutic plasma exchange procedure was observed. The outcome of treatment was complete recovery in 38 (88.4%) patients. Conclusion: Therapeutic plasma exchange can be used as an important treatment method in critically ill patients in pediatric intensive care units. The procedure can be safely performed in children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Febrile neutropenia (FN) is a common and life-threatening complication that develops during therapy for childhood cancer. Serious bacterial illness is a significant cause of morbidity and mortality for neutropenic patients The primary objective of the study was to determine etiology and clinical course of fever in neutropenic children with cancer. The aim was to identify the risk of development of invasive bacterial infection (IBI) and factors associated with mortality in pediatric cancer FEN patients. Method: This study was conducted in University of Health Sciences, Ankara Child Health and Diseases Hematology Oncology Training and Research Hospital between January 2006 and and December 2013. Invasive bacterial infections and related mortality in children aged 0 to 18 years of age were documented. Results: A total of 325 neutropenic febrile episodes of 134 patients were evaluated. The most common preexisting risk factor for invasive bacterial infection was acute myeloid leukemia phenotyp. Other risk factors included, thrombocytopenia, bloodstream infection, C-reactive protein value >9 mg/dL and pneumoniae. In our case series overall infection- associated mortality was found as 4% similar as in the literature. Conclusion: Invasive bacterial infections is still be major cause of mortality and morbidity for pediatric leukemia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Objective: Folic acid-related genes' polymorphisms have been related with a predisposition to acute lymphoblastic leukemia (ALL). Two common polymorphic sites on MTHFR gene; T677T and C1298C may decrease the activity of this enzyme compared to the wild type alleles (C677C and A1298A). The polymorphism may affect the metabolism of antifolate drugs and cause increased drug toxicity and decreased survival. In this study, we evaluated the effect of two frequent polymorphisms on survival of children with ALL. Material and Methods: We retrospectively evaluated patients who had been diagnosed with B cell ALL and then treated with the BFM TRALL 2000 treatment protocol. We recorded their absolute blast counts at day 8, and bone marrow evaluation at days 15 and 33 as well as MTHFR polymorphisms. results: Fifty-six patients [male/female: 33/23, mean age at diagnosis 4.73 years range 1.3-16.75 years)] were included in the study. Out of the 56 patients, 5 developed relapse. There was no relationship between different polymorphic alleles of the MTHFR gene with survival and event-free survival. conclusion: We did not observe any effect of MTHFR polymorphisms on survival of children with ALL. We believe further studies with a larger group of patients are necessary to draw a firm conclusion. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 3 day G-CSF priming, we achieved the same number of CD34+ cells per recipient’s weight in 2 day 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 3 day 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 (≤10 year) 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Wolfram syndrome is a genetic condition, which is inherited in autosomal recessive form and characterized by the combination of diabetes mellitus, optic atrophy, diabetes insipidus and deafness. Bleeding tendency in Wolfram syndrome was noted but a predisposition to thrombosis has not been reported previously. We present two siblings with Wolfram syndrome and recurrent thrombosis. Two girls (13 and 12 years old) with Wolfram syndrome were referred to our clinic because of recurrent thrombotic attacks after each attempt to open venovenous fistulas. Tests were performed to determine the patients' predisposition to thrombosis. Anti-thrombin III, protein C and S, lipoprotein (a), lupus anticoagulant, anticardiolipin IgG and IgM were within the normal range. Genetic analysis showed that factor V Leiden 1691 G>A and factor II (prothrombin) 20210 G>A were homozygous normal and MTHFR C677T gene mutation was heterozygous for each patient. No thrombosis attack was observed after adequate heparinization. Predisposition to thrombosis is a newly feature in Wolfram syndrome, as thrombosis with this syndrome has never been reported. [ABSTRACT FROM AUTHOR]