Venous thromboembolism in children with cancer – a population-based cohort study

Introduction: Cancer is a known risk factor for venous thromboembolism (VTE) in adults, but population-based data in children are scarce. Materials and methods: We conducted a cohort study utilising linkage of the Clinical Practice Research Database (primary care), Hospital Episodes Statistics (secondary care), UK Cancer Registry data and Office for National Statistics cause of death data. From these databases, we selected 498 children with cancer diagnosed between 1997 and 2006 and 20,810 controls without cancer. We calculated VTE incidence rates in children with cancer vs. controls, and hazard ratios (HRs) using Cox regression. Results: We identified four VTE events in children with cancer compared with four events in the larger control population corresponding to absolute risks of 1.52 and 0.06 per 1000 person-years respectively. The four children with VTE and cancer were diagnosed with hematological, bone or non-specified cancer. Childhood cancer was hence associated with a highly increased risk of VTE (HR adjusted for age and sex: 28.3; 95%CI = 7.0-114.5). Conclusions: Children with cancer are at increased relative risk of VTE compared to those without cancer. Physicians could consider thromboprophylaxis in children with cancer to reduce their excess risk of VTE however the absolute risk is extremely small and the benefit gained therefore would need to be balanced against the risk invoked of implementing such a strategy. Novelty & Impact Statements: While there is a reasonable level of knowledge about the risk of VTE in adult populations, it is not well known whether this risk is reflected in paediatric patients. We found a substantial increase in risk of VTE in children with cancer compared to a child population without cancer. While this finding is important, the absolute risk of VTE is still low and must be balanced with the risks of anticoagulation

Normal karyotype is a poor prognostic factor in Myeloid Leukemia of Down Syndrome: a retrospective international study

Myeloid leukemia of Down Syndrome has a better prognosis than sporadic pediatric acute myeloid leukemia. Most myeloid leukemia of Down syndrome cases are characterized by additional cytogenetic changes besides the constitutional trisomy 21, but their potential prognostic impact is not known. We therefore conducted an international retrospective study of clinical characteristics, cytogenetics, treatment, and outcome of 451 children with myeloid leukemia of Down syndrome . All karyotypes were centrally reviewed before assigning patients to subgroups. The overall 7-year event-free survival for the entire cohort was 78% (+/-2%), with overall survival 79% (+/-2%), cumulative incidence of relapse 12% (+/-2%), and cumulative incidence of toxic death 7% (+/-1%). Outcome estimates showed large differences across the different cytogenetic subgroups. Based on the cumulative incidence of relapse , we could risk-stratify patients into two groups: normal karyotype cases (n=103) with a higher cumulative incidence of relapse (21% (+/-4%)) than cases with an aberrant karyotype (n=255) with a cumulative incidence of relapse of 9% (+/-2%) (p=0.004). Multivariate analyses revealed white blood cell counts >/=20 x109/l and age >3 years as independent predictors for poor event-free survival event-free survival, while normal karyotype independently predicted inferior overall survival, event-free survival, and relapse-free survival. In conclusion, this study showed large differences in outcome within Myeloid leukemia of Down Syndrome patients and identified novel prognostic groups that predicted clinical outcome and hence may be used for stratification in future treatment protocols