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 cases of myeloid leukemia of Down syndrome 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 the overall survival rate being 79% (± 2%), the cumulative incidence of relapse 12% (± 2%), and the 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: cases with a normal karyotype (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 that white blood cell count ≥ 20 × 10(9)/L and age >3 years were independent predictors for poor 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 patients with myeloid leukemia of Down syndrome and identified novel prognostic groups that predicted clinical outcome and hence may be used for stratification in future treatment protocols.

[COVID-19-associated hyperinflammatory state in a 15-year-old female patient]. / Covid-19-geassocieerde hyperinflammatie.

Paediatric Multisystem Inflammatory Syndrome Temporally Related to SARS-CoV-2 (PIMS-TS) is a rare novel clinical entity observed in children and adolescents with evidence of a recent COVID-19 infection, and is characterized by a marked hyperinflammatory state with involvement of multiple organ systems.We report a case of a previously healthy 15-year-old female patient, who was admitted to paediatric intensive care with cardiac failure and was subsequently shown to have positive COVID-19 serology. The presenting symptoms were fever, cough, chest pain and gastro-intestinal symptoms. She was supported with milrinone and a low dose of vasopressors. Her hyperinflammatory state was treated with intravenous immunoglobulins, high dose aspirin and high-dose methylprednisolone. PIMS-TS is a rare, potentially life threatening novel clinical entity in children and adolescents with evidence of a COVID-19 infection. Clinicians need to be aware of the possibility of this new disease, to ensure prompt recognition and treatment.

Somatic thrombopoietin (THPO) gene mutations in childhood myeloid leukemias.

We report, for the first time, a non-syndromic infant with a reversible myeloproliferative disease that harbors a germline hereditary thrombopoietin (THPO) gene mutation, a condition that is known to induce familial thrombocytosis at increasing age. In order to investigate whether somatic THPO gene mutations play a role in sporadic pediatric myeloproliferative diseases, we performed a mutation screening of a large representative cohort of pediatric acute myeloid leukemia, myeloid leukemia of Down syndrome, and juvenile myelomonocytic leukemia samples and show that gain-of-function THPO mutations are extremely rare in sporadic pediatric myeloproliferative diseases.

Use of complementary and alternative medicine by pediatric patients with functional and organic gastrointestinal diseases: results from a multicenter survey.

OBJECTIVES: Many pediatric patients use complementary and alternative medicine, especially when facing a chronic illness for which treatment options are limited. So far, research on the use of complementary and alternative medicine in patients with functional gastrointestinal disease has been scarce. This study was designed to assess complementary and alternative medicine use in children with different gastrointestinal diseases, including functional disorders, to determine which factors predicted complementary and alternative medicine use and to assess the willingness of parents to participate in future studies on complementary and alternative medicine efficacy and safety. PATIENTS AND METHODS: The prevalence of complementary and alternative medicine use was assessed by using a questionnaire for 749 children visiting pediatric gastroenterology clinics of 9 hospitals in the Netherlands. The questionnaire consisted of 35 questions on the child's gastrointestinal disease, medication use, health status, past and future complementary and alternative medicine use, reasons for its use, and the necessity of complementary and alternative medicine research. RESULTS: In this study population, the frequency of complementary and alternative medicine use was 37.6%. A total of 60.3% of this group had used complementary and alternative medicine specifically for their gastrointestinal disease. This specific complementary and alternative medicine use was higher in patients with functional disorders than organic disorders (25.3% vs 17.2%). Adverse effects of allopathic medication, school absenteeism, age