COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group.

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.

Thromboembolism in Children.

OBJECTIVE: To study pediatric patients who were diagnosed with thrombosis between January 2009 and March 2020. METHODS: Patients were evaluated with respect to thrombophilic risk factors, localization of the thrombus, response to treatment, and recurrence rates during the last 11 y. RESULTS: Among 84 patients, 59 (70%) had venous thrombosis and 20 (24%) had arterial thrombosis. The number of documented thrombosis amongst hospitalized children in authors' hospital has increased over the years. It has been observed that the annual incidence of thromboembolism has increased after 2014. Thirteen patients were recorded between 2009 and 2014 and 71 patients between 2015 and 2020 (until March 2020). Exact thrombosis localization could not be detected in 5 patients. The median age of patients was 8 ± 5.95 (range 0-18). Fourteen children (16.9%) had a history of familial thrombosis. Genetic and/or acquired risk factors were detected in 81 (96.4%) of the patients. Overall, 64 patients (76.1%) had acquired risk factors such as infection (20.2%), catheterization (13.1%), liver disease (11.9%), mastoiditis (8.3%), liver transplantation (6%), hypoxic-ischemic encephalopathy (4.8%), dehydration (3.6%), trauma (3.6%) and cancer (2.4%). As genetic risk factors, the most common genetic mutations were PAI-1 4G>5G, MTHFR C677T, and MTHFR A1298C mutations. Twenty-eight (41.2%) patients had at least one genetic thrombophilic mutation. At least one homozygous mutation in 37 patients (44%) and at least one heterozygous mutation in 55 patients (65.4%) were detected. CONCLUSIONS: The annual incidence of thrombosis has increased over the years. Genetic predisposition and acquired risk factors play an important role in etiology, treatment, and follow-up in children with thromboembolism. Especially, genetic predisposition is common. Thrombophilic risk factors should be investigated and optimal therapeutic and prophylactic measures should be promptly taken in children with thrombosis.

Hematopoietic stem cell transplantation activities and HRQOL of refugee or asylum seeker children in Turkey: A multicenter study.

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

Intensive chemotherapy perturbs heart rate variability in children with cancer.

OBJECTIVES: In children, cancer chemotherapy may impair the functioning of the cardiac autonomic nervous system. Moreover, it is not known whether there are any differences between intensive and maintenance phases of chemotherapy. Therefore, the aim of the current study was to assess autonomic nervous system activity using heart rate variability, in children receiving intensive or maintenance cancer chemotherapy. METHODS: For that purpose, children who were healthy (healthy control, n = 30), receiving intensive chemotherapy (chemotherapy, n = 30), and receiving maintenance chemotherapy (maintenance, n = 25) were included in the study. Autonomic nervous system activity was measured by means of heart rate variability. Electrocardiogram recordings were used to calculate time- and frequency-domain heart rate variability parameters. RESULTS: Time-domain parameters such as standard deviation of NN intervals and frequency-domain parameters such as total power were lower during the intensive chemotherapy but not during maintenance phase (standard deviation of NN intervals: 50±5, 33±3, and 48±3 ms, and total power: 2613±504, 1379±296 and 2295±264 ms2, respectively for healthy control, chemotherapy and maintenance groups, P<0.001 for both standard deviation of NN intervals and total power). DISCUSSION: The present results indicate that intensive chemotherapy perturbs the function of heart rate variability in children, with recovery during the maintenance phase. This suggests that intensive chemotherapy is likely to affect the autonomic nervous system but this effect does not appear to be permanent.

Results of multicenter registry for patients with inherited factor VII deficiency in Turkey.

INTRODUCTION: Inherited factor VII (FVII) deficiency (FVIID) is the most common of inherited rare bleeding disorders. Other determinants of clinical severity apart from FVII level (FVIIL) include genetic and environmental factors. We aimed to identify the cut-off FVIILs for general and severe bleedings in patients with FVIID by using an online national registry system including clinical, laboratory, and demographic characteristics of patients. METHODS: Demographic, clinical, and laboratory data of patients with FVIID extracted from the national database, constituted by the Turkish Society of Hematology, were examined. Bleeding phenotypes, general characteristics, and laboratory features were assessed in terms of FVIILs. Bleeding rates and prophylaxis during special procedures/interventions were also recorded. RESULTS: Data from 197 patients showed that 46.2% of patients had FVIIL< 10%. Most bleeds were of mucosal origin (67.7%), and severe bleeds tended to occur in younger patients (median age: 15 (IQR:6-29)). Cut-off FVIILs for all and severe bleeds were 16.5% and 7.5%, respectively. The major reason for long-term prophylaxis was observed as central nervous system bleeding (80%). CONCLUSION: Our data are consistent with most of the published literature in terms of cut-off FVIIL for bleeding, as well as reasons for prophylaxis, showing both an increased severity of bleeding and younger age at diagnosis with decreasing FVIIL. However, in order to offer a classification similar to that in Hemophilia A or B, data of a larger cohort with information about environmental and genetic factors are required.

Erythrocyte transfusion restored heart rate variability in children with thalassemia major.

Thalassemia major (TM) is a severe transfusion-dependent anemia. Regular erytrocyte transfusion is required for the treatment of thalassemia patients. However, repeated transfusion may result in impairements in heart function. In this study, we aimed to investigate short-term effects of erythrocyte transfusion on autonomic control of heart in children with thalassemia major. For that purpose heart rate variability (HRV), which is a non-invasive method used to evaluate the effects of the autonomic nervous system on the heart rhythym, was measured before and after erythrocyte transfusion and compared to the healthy controls. Children diagnosed with TM (n = 17) and sex and age matched healthy children (HC, n = 30) were included in the study. HRV values of TM patients were measured 5 min before erythrocyte transfusion (BET, n = 17) and 5 min after erythrocyte transfusion (AET, n = 17). Parameters of time-domain and frequency-domain of HRV were evaluated in all participants. Heart rate (HR) was higher in the BET than AET (P = 0.002) but there was no difference between AET and HC groups (P > 0.05). HRV parameters were lower in BET than AET (P < 0.05) but there were no statistical difference between AET and HC (P> 0.05). The data suggest that, in thalassemia major patients, erythrocyte transfusion restores HR and HRV parameters to the levels observed in healthy controls and, thus, in short-terms, appears to be beneficial for the autonomic control of the heart.