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De Montalembert M.,Necker Childrens Hospital | De Montalembert M.,Laboratory of Excellence GR Ex | Ribeil J.-A.,Necker Childrens Hospital | Ribeil J.-A.,French Institute of Health and Medical Research | And 25 more authors.
PLoS ONE | Year: 2017

The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2∗<20 ms, in patients with thalassemia, SCA, or MDS. Patient inclusion criteria were an accurate record of erythrocyte concentrates (ECs) received, a transfusion history >8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2∗was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001). Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001). Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation. © 2017 de Montalembert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


von Laer Tschudin L.,University of Lausanne | Schwitzgebel V.M.,Pediatric Endocrine and Diabetes Unit | von Scheven-Gete A.,Rhumatologie Pediatrique Romande | Hofer M.,Rhumatologie Pediatrique Romande | And 4 more authors.
Pediatric Diabetes | Year: 2015

Type 1 diabetes (T1D) is rarely a component of primary immune dysregulation disorders. We report two cases in which T1D was associated with thrombocytopenia. The first patient, a 13-year-old boy, presented with immune thrombocytopenia (ITP), thyroiditis, and, 3 wk later, T1D. Because of severe thrombocytopenia resistant to immunoglobulins, high-dose steroids, and cyclosporine treatment, anti-cluster of differentiation (CD20) therapy was introduced, with consequent normalization of thrombocytes and weaning off of steroids. Three and 5 months after anti-CD20 therapy, levothyroxin and insulin therapy, respectively, were stopped. Ten months after stopping insulin treatment, normal C-peptide and hemoglobin A1c (HbA1c) levels and markedly reduced anti-glutamic acid decarboxylase (GAD) antibodies were measured. A second anti-CD20 trial for relapse of ITP was initiated 2 yr after the first trial. Anti-GAD antibody levels decreased again, but HbA1c stayed elevated and glucose monitoring showed elevated postprandial glycemia, demanding insulin therapy. To our knowledge, this is the first case in which insulin treatment could be interrupted for 28 months after anti-CD20 treatment. In patient two, thrombocytopenia followed a diagnosis of T1D 6 yr previously. Treatment with anti-CD20 led to normalization of thrombocytes, but no effect on T1D was observed. Concerning the origin of the boys' conditions, several primary immune dysregulation disorders were considered. Thrombocytopenia associated with T1D is unusual and could represent a new entity. The diabetes manifestation in patient one was probably triggered by corticosteroid treatment; regardless, anti-CD20 therapy appeared to be efficacious early in the course of T1D, but not long after the initial diagnosis of T1D, as shown for patient two. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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