Sirolimus is effective and safe in childhood relapsed-refractory autoimmune cytopenias: A multicentre study.

Autoimmune cytopenias are a heterogeneous group of disorders characterized by immune-mediated destruction of haematopoietic cell lines. Effective and well-tolerated treatment options for relapsed-refractory immune cytopenias are limited. In this study, the aim was to evaluate the efficacy and safety of sirolimus in this disease group within the paediatric age group. The study enrolled patients in the paediatric age group who used sirolimus with a diagnosis of immune cytopenia between December 2010 and December 2020, followed at six centres in Turkey. Of the 17 patients, five (29.4%) were treated for autoimmune haemolytic anaemia (AIHA), six (35.2%) for immune thrombocytopenic purpura (ITP) and six (35.2%) for Evans syndrome (ES). The mean response time was 2.7 months (range, 0-9 months). Complete response (CR) and partial response (PR) were obtained in 13 of 17 patients (76.4%) and nonresponse (NR) in four patients (23.5%). Among the 13 patients who achieved CR, three of them were NR in the follow-up and two of them had remission with low-dose steroid and sirolimus. Thus, overall response rate (ORR) was achieved in 12 of 17 patients (70.5%). In conclusion, sirolimus may be an effective and safe option in paediatric patients with relapsed-refractory immune cytopenia.

Efficacy of Teicoplanin Lock Therapy in the Treatment of Port-related Coagulase-negative Staphylococci Bacteremia in Pediatric Oncology Patients.

The number of studies evaluating teicoplanin lock therapy in coagulase-negative staphylococcus-associated catheter infection in pediatric malignancies is limited. The aim of this study was to evaluate the efficacy of teicoplanin lock therapy in pediatric cancer cases. Twenty-two patients with coagulase-negative staphylococcus-associated totally implantable venous access device infection, who had undergone teicoplanin closure treatment, were included in the study. Demographic data, number of lock treatment days, and treatment success data were obtained from the medical files of the patients. Fourteen of the patients (63.6%) had acute lymphocytic leukemia, 3 (13.6%) had acute myelocytic leukemia, and 5 (22.7%) had solid cancer. The median neutrophil count was 240×10 3 /µL (interquartile range: 0 to 1195×10 3 /µL). Between patients with and without catheter removal, no statistically significant difference was found in terms of baseline C-reactive protein, absolute neutrophil count, and the day of starting systemic teicoplanin treatment ( P >0.05). The overall port survival rate of teicoplanin lock therapy was 72.7%. Within an average of 4 days, negative cultures of 16 (72.7%) patients whose catheters had not been removed were obtained. In conclusion, we suggest that teicoplanin lock therapy is an effective and safe treatment for catheter-related infections, caused by methicillin-resistant coagulase-negative staphylococcus.

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study.

BACKGROUND: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. MATERIALS AND METHODS: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 ). RESULTS: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. CONCLUSION: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.

Assessment of clinical characteristics and treatment outcomes of pediatric patients with intracardiac thrombosis: a single-center experience.

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

Evaluation of renal effects of liposomal amphotericin B in children with malignancies with KDIGO and RIFLE criteria.

BACKGROUND: Amphotericin B is a broad-spectrum antifungal agent and is the backbone of the treatment for medically important opportunistic fungal pathogens in children. This study aimed to compare the nephrotoxicity associated with L-AmB in children with acute lymphoblastic leukemia and acute myeloid leukemia. MATERIALS AND METHODS: A total of 112 pediatric acute lymphoblastic leukemia or acute myeloid leukemia patients who received treatment with L-AmB (Ambisome®) at the University of Health Sciences Dr Behcet Uz Children's Hospital over 7 years were included. The incidence of hypokalemia, decreased estimated glomerular filtration rate and presence of acute kidney injury was recorded. RESULTS: The average L-AmB treatment duration was 17.1±15.0 days. Five patients (4.4%) of the patients had grade I acute renal injury according to KDIGO criteria and 16 patients (14.2%) had increased risk for kidney injury according to RIFLE criteria. There were no patients with eGFR decrease above 50% and no renal injury and failure were observed during L-AmB treatment. The rate of patients with hypokalemia in the pre-treatment was 17.9% and the post-L-AmB group was 50.0%. The rate of hypokalemia was higher in the post-treatment group (P=0.0015). Among the 112 patients, only two patients (1.7%) required cessation of L-AmB treatment due to resistant hypokalemia despite supplementation. CONCLUSIONS: Hypokalemia was more common compared to glomerulotoxicity and acute renal injury (according to KDIGO and RIFLE criteria) in pediatric leukemia patients treated with L-AmB. Hypokalemia developed in nearly half of the patients and the study shows the need for randomized controlled trials and strategies for hypokalemia associated with L-AmB treatment.

Influenza-related hospitalizations due to acute lower respiratory tract infections in a tertiary care children's hospital in Turkey.

BACKGROUND: The influenza virus is a significant cause of acute lower respiratory tract infections (LRTI) requiring hospitalization in childhood and leads to severe morbidity and mortality, especially in certain risk groups. OBJECTIVES: The study aims to evaluate acute LRTI due to influenza in a tertiary care hospital and the risk factors for hospitalization among Turkish children. STUDY DESIGN: Children between 1 month and 18 years of age who were hospitalized at Dr. Behçet Uz Children's Hospital between January 2016 and March 2018 with lower respiratory tract infection that tested positive for influenza by PCR were included. Children with viral coinfections were excluded. Patient files were retrospectively scanned from the hospital computerized system in terms of age, underlying diseases, whether antiviral therapy was used, and length of hospital stay. Statistical analysis was performed using SPSS statistical software. RESULTS: The study included 131 patients with a median age of 2 years (1 month-15 years). Sixty-seven (51,1%) patients were younger than two years. Influenza A was isolated in 129 patients and B in 2 patients. Fifty-two patients (39,7%) had underlying medical conditions, and the most common one was malignancies (12/52, 23%). This was followed by neurodevelopmental diseases (9/52, 17,3%), prematurity (9/52 patients, 17,3%), primary immunodeficiency (8/52, 15,4%), asthma (7/52, 13,4%), Down syndrome (4/52, 7,7%), chronic renal disease (2/52, 3,8%) and congenital heart diseases (1/52, 1,9%). The mean length of stay (LOS) was 12,3 ± 9,5 days (2-60 days). The LOS was found to be statistically longer (15,2 ± 12,1 days, 3-60 days) in patients with an underlying disease compared to previously healthy patients (10,4 ± 6,7 days, 2-35 days) (p = 0.01). CONCLUSIONS: Hospitalization due to influenza-related acute LRTI is not an issue only for patients with an underlying medical condition. Vaccination should be considered not only for those with underlying medical conditions but also for healthy children.

Correction to: Central line bundle including split-septum device and single-use prefilled flushing syringes to prevent port-associated bloodstream infections: a cost and resource-utilization analysis.

An amendment to this paper has been published and can be accessed via the original article.

Central line bundle including split-septum device and single-use prefilled flushing syringes to prevent port-associated bloodstream infections: a cost and resource-utilization analysis.

BACKGROUND: Central line bundle programs were found to be effective in decreasing central line-associated bloodstream infection rates in pediatric cancer patients with ports. However, cost-effectiveness studies of central line bundle programs in pediatric cancer patients are limited, and most available data are from intensive care unit or adult studies. METHODS: In this cross-sectional study spanning 6 years, comprehensive assessment of total health care costs attributable to CLABSI's associated with ports between two periods. RESULTS: This cross-sectional study was carried out in the pediatric hematology-oncology ward of Dr. Behçet Uz Children's Hospital from 1 August November 2011 to 31 July 2017. The CLABSI rates decreased significantly from 8.31 CLABSIs to 3.04 per 1000 central line days (p < 0.001). In the pre-bundle period, total attributable costs spent for of patients with CLABSI were $130,661, and in the bundle period, total attributable costs spent for patients with CLABSI were $116,579. Within bundle implantation, 71 potential CLABSI were prevented, which saved an additional $208,977. CONCLUSION: Our study shows that central line bundles decreases not only the CLABSI rate but also decreases attributable costs due to CLABSI. Expenses spent for bundle elements, were covered by savings by preventing CLABSI with higher costs.

Evaluation of Liver Iron Content by Magnetic Resonance Imaging in Children with Acute Lymphoblastic Leukemia after Cessation of Treatment

Objective: There are a limited number of studies evaluating iron overload in childhood leukemia by magnetic resonance imaging (MRI). The aim of this study was to determine liver iron content (LIC) by MRI in children with acute lymphoblastic leukemia (ALL) who had completed treatment and to compare those values with serum iron parameters. Materials and Methods: A total of 30 patients between the ages of 7 and 18 who had completed ALL treatment were included in the study. Serum iron parameters (serum iron, serum ferritin [SF], and total iron-binding capacity) and liver function tests were studied. R2 MRI was performed for determining LIC. Results: Normal LIC was detected in 22 (63.4%) of the cases. Seven (23.3%) had mild and 1 (3.3%) had moderate liver iron deposition. In contrast, severe iron overload was not detected in any of the cases. LIC levels were correlated with the numbers of packed red blood cell (pRBC) transfusions (r=0.637, p<0.001), pRBC transfusion volume (r=0.449, p<0.013), SF levels (r=0.561, p=0.001), and transferrin saturation (r=0.353, p=0.044). In addition, a positive correlation was found between the number of pRBC transfusions and SF levels (r=0.595, p<0.001). Conclusion: We showed that the frequency of liver iron deposition was low and clinically less significant after the end of treatment in childhood ALL patients. LIC was demonstrated to be related to SF and transfusion history. These findings support that SF and transfusion history may be used as references for monitoring iron accumulation or identifying cases for further examinations such as MRI.

Assessment of Serum Galactomannan Test Results of Pediatric Patients With Hematologic Malignancies According to Consecutive Positivity and Threshold Level in Terms of Invasive Aspergillosis Diagnosis: Cross-Sectional Research in a Tertiary Care Hospital.

The aim of this study was to evaluate the diagnostic utility of serum galactomannan (GM) positivity for invasive aspergillosis (IA) in children. Positive GM results between January 2015 and August 2017 were reviewed retrospectively in children with hematologic malignancies. Single and consecutive positive GM results were evaluated according to the different galactomannan index (GMI) (>0.5, >0.7, >1.0 and >1.5) values. There were 104 positive GM results of 70 patients. IA was identified in 29 patients (41.4%) (2 proven and 27 probable). For a single positive GMI of >0.5, >0.7, >1.0, and >1.5, the numbers were 104, 76, 57, and 32 and the positive predictive values (PPVs) were 39.4%, 43.2%, 47.2%, and 50.0%, respectively. The single GM positivity at different thresholds showed no difference between the IA and non-IA group (P>0.05). For 2 consecutive positive GMI values of >0.5, >0.7, >1.0, and >1.5, the numbers were 34, 20, 13, and 4, and the PPVs were 58.8%, 65.0%, 84.6%, and 100.0%, respectively. In the IA group, positivity was higher at all thresholds (P<0.05). According to our findings, consecutive GM positivity has higher PPVs independently from the cutoff value chosen. In pediatric patients with high risk, consecutive sampling should be preferred.

A 3-Year Retrospective Study of the Epidemiology of Acute Respiratory Viral Infections in Pediatric Patients With Cancer Undergoing Chemotherapy.

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