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There is conflicting information about the epidemiology of thromboembolism (TE) in paediatric oncology. Objectives were to describe the incidence and risk factors of TE in children with cancer. We included all children with cancer less than 15 years of age diagnosed from 2001 to 2016, treated at one of the 12 Canadian paediatric centres outside of Ontario and entered into the Cancer in Young People-Canada database. Potential risk factors for TE were evaluated using Cox proportional hazards regression stratified by haematological malignancies versus solid tumours. Factors associated with vascular access- and non-vascular access-related TE were compared using chi-square or Fisher's exact tests. Of the 7,471 children included, 283 experienced TE requiring medical intervention; cumulative incidence of TE at 5 years was 3.8 ± 0.2% and 0.36% ± 0.07% for life-threatening or fatal TE. For haematological malignancies, the following factors were associated with TE in multivariable regression: age < 1 year, 5 to 9.99 years and 10 to 14.99 years (relative to age 1-4.99 years), haematopoietic stem cell transplant (hazard ratio [HR] = 1.49, 95% confidence interval [CI], 1.00-2.32), anthracyclines (HR = 2.21, 95% CI, 1.12-4.37) and asparaginase (HR = 1.68, 95% CI, 1.15-2.44). For solid tumours, obesity (HR = 1.92, 95% CI, 1.01-3.68), surgery (HR = 2.70, 95% CI, 1.44-5.08), radiation (HR = 47.51, 95% CI, 24.01-94.01), anthracyclines (HR = 2.74, 95% CI, 1.29-5.82) and platinum agents (HR = 2.26, 95% CI, 1.19-4.28) were associated with TE. Life-threatening and fatal TEs were more common among non-vascular access TEs (14.5% vs. 3.3% = 0.001). In a population-based cohort, 4% of children with cancer developed a clinically significant TE. Accurate risk stratification tools are needed specific to malignancy type.

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Thromboembolism (TE) is a well-recognized complication of pediatric cancer and can lead to mortality and excess morbidity. There is conflicting evidence about the effectiveness and safety of thromboprophylaxis in children. We conducted a systematic literature review and network meta-analysis of primary pharmacological thromboprophylaxis in children and adolescents (0–21 years) with cancer. The primary outcomes were objectively proven TE and major bleeding. The network meta-analysis included comparisons of multiple alternatives simultaneously: antithrombin (AT) replacement, low molecular weight heparin (LMWH), vitamin K antagonists (VKAs), and standard of care (SOC) defined as no thromboprophylaxis or low-dose heparin for catheter patency. Six articles describing 1,318 patients were included (mean age: 6.7 years, 56.7% male). Acute lymphoblastic leukemia was the underlying diagnosis in 97.5% of patients. All studies were considered at moderate or high risk of bias. LMWH was the only agent associated with lower odds of TE compared with SOC (odds ratio [OR]: 0.23, 95% confidence interval [CI]: 0.06–0.81). No statistically significant difference was detected between other thromboprophylaxis modalities and SOC. Tau2 and I 2 suggested a high degree of heterogeneity. No statistically significant differences in the odds of major bleeding were found between AT replacement, LMWH, VKA, and SOC. Current evidence suggests that low-dose LMWH is effective and safe to prevent TE in children with cancer but is insufficient to conclude if AT replacement or VKA are effective thromboprophylaxis options. Further research, notably randomized controlled trials enrolling children with diverse types of cancer, is crucially needed.

Acquired von Willebrand syndrome (AVWS) is reported in high-flow high-shear congenital cardiac disorders. We hypothesized that the narrowed pulmonary vasculature in idiopathic pulmonary arterial hypertension (IPAH) may induce AVWS. We conducted a cross-sectional evaluation of children with IPAH. Patients with bleeding symptoms and/or laboratory abnormalities (thrombocytopenia, anomalies in coagulation screening tests) were tested in-depth for haemostatic defects. Fourteen children were followed with IPAH of which 8 were eligible. Four children exhibited abnormal bleeding scores (International Society on Thrombosis and Haemostasis Bleeding Assessment Tool: 3-5). All 8 patients showed very prolonged platelet function analyser (PFA)-100 closure times. Six children demonstrated either mild thrombocytopenia or low-normal von Willebrand factor (VWF) antigen (VWF:Ag) or VWF activity [mean (range), in iu/dl: VWF:Ag: 70 (61-91); VWF activity: 57 (34-70)]. Average VWF collagen binding capacity (VWF:CB) was 64 iu/dl (range: 53-123 iu/dl), with low-normal VWF activity/VWF:Ag or VWF:CB/VWF:Ag ratios occurring in five patients. All children had normal multimers distribution patterns. One patient underwent a lung transplantation, with normalization of haemostatic abnormalities post-surgery. Overall, 8 out of 14 children with IPAH had mild to moderate bleeding symptoms and/or laboratory abnormalities in keeping with AVWS. Normalization of the haemostatic defects following lung transplantation and lack of family history of bleeding attests to the acquired nature of their defects.

Children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been consistently described with milder clinical outcomes compared to adults. [1][2][3] Whereas increased rates of severe illness and death have been reported in adults with cancer and concurrent SARS-CoV-2 infection, 4-7 previous studies in pediatric cancers have yielded conflicting results with regards to infection outcomes. [8][9][10][11] Herein, we report the baseline characteristics and clinical outcomes of 31 pediatric oncology patients who were diagnosed with SARS-CoV-2 infection at the four pediatric oncology centers in the

PURPOSE Infections are a frequent complication during childhood leukemia treatment. Little is known about the infectious risk in survivors. We compared the relative rate (RR) of infections after treatment completion between pediatric leukemia survivors and the general population. METHODS We performed a retrospective, population-based cohort study of children diagnosed with leukemia between 1992 and 2015 in Ontario, Canada, who were alive and relapse free 30 days after treatment completion (index date). Leukemia survivors were matched 5:1 with the general population by year of birth, sex, and rural status and stratified by initial treatment, including and excluding hematopoietic stem-cell transplantation (HSCT). The primary outcome was time to infections, as identified using validated diagnostic codes from administrative databases. Individuals were censored at the earliest of death, first relapse, loss to follow-up, or end of study. RESULTS A total of 2,204 leukemia survivors were included and matched with 11,020 controls. The rate of infections was elevated after treatment completion compared with controls (RR, 1.51; 95% CI, 1.45 to 1.57) and at less than 1 year (RR, 1.77; 95% CI, 1.69 to 1.86); 1 to 4.99 years (RR, 1.66; 95% CI, 1.62 to 1.71), and 5 or more years (RR, 1.29; 95% CI, 1.22 to 1.36) from the index date. Among those whose initial treatment excluded HSCT, the rate remained elevated more than 5 years from the index date (RR, 1.29; 95% CI, 1.23 to 1.35). Infection-related death was significantly increased in leukemia survivors both among the entire cohort (hazard ratio, 149.3; 95% CI, 20.4 to 1,091.9) and among those without HSCT (hazard ratio, 92.7; 95% CI, 12.4 to 690.7). CONCLUSION A significant association was found between a history of leukemia therapy and an increased risk of infections. Additional study is needed to establish which exposures in patients with leukemia lead to late infections.

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