Gastric ulcer in a child treated with deferasirox.

We present a patient with thalassemia major who developed a gastric ulcer, probably related to the use of deferasirox. Although gastric ulcer is mentioned as infrequent adverse event in the scientific product information of deferasirox, in our current knowledge, this is the first case-report on this adverse drug reaction. The severity of this event justifies the reporting of this case.

Hydroxyurea for sickle cell disease in children and for prevention of cerebrovascular events: the Belgian experience.

Hydroxyurea (HU) is considered to be the most successful drug therapy for severe sickle cell disease (SCD). Nevertheless, questions remain regarding its benefits in very young children and its role in the prevention of cerebrovascular events. There were 127 SCD patients treated with no attempt to reach maximal tolerated doses who entered the Belgian Registry: 109 for standard criteria and 18 who were at risk of stroke only. During 426 patient-years of follow-up for patients with standard criteria, 3.3 acute chest syndromes, 1.3 cerebrovascular events, and 1.1 osteonecrosis per 100 patient-years were observed. A subgroup of 32 patients followed for 6 years experienced significant benefit over this period. In each subgroup of children (younger than 2 years, 2-5, 6-9, and 10-19 years) followed for 2 years, clinical and biologic changes were similar, except for children younger than 2 years who had no total hemoglobin increase and remained at risk of severe anemia. In 72 patients evaluated by transcranial Doppler studies (TCD), 34 patients were at risk of primary stroke and only 1 had a cerebrovascular event after a follow-up of 96 patient-years. These results confirm the benefit of HU, even in very young children, and its possible role in primary stroke prevention.

Familial and congenital polycythemias: a diagnostic approach.

The rare absolute polycythemias with an innate and hereditary character can be grouped together under the heading "familial and congenital polycythemias" (FCPs). Primary forms, due to an intrinsic defect in the erythroid progenitor cells, and secondary forms, resulting from extrinsic factors such as an elevated erythropoietin level, have both been reported. Despite the widely divergent characteristics of the different FCPs, the range of possible diagnoses is much more restricted and the distribution of disorders markedly different compared with polycythemias in general. Therefore, in FCP, one can argue against following the algorithm of the Polycythemia Vera Study Group for the evaluation of an elevated hematocrit level, following instead a more specific algorithm. In this article the authors describe a child with primary FCP, review the different FCPs, and propose an adapted work-up scheme.

Neutralizing antibodies in gene-defective hosts.

In a host with a normal immune system and a complete gene defect, the nondefective gene product will be immunogenic. Consequently, neutralizing antibodies against the respective protein can arise either 'spontaneously' or after immunization, as shown in patients and in animal models, such as knockout mice. Accordingly, patients with X-linked or homozygous autosomal gene defects are at risk of developing neutralizing antibodies, in particular after protein substitution or gene therapy. This Review compares and exemplifies the various genetic and immunological contexts that lead to 'neutralizing and generated by gene defect' or 'nagged' antibodies, and outlines implications and solutions for therapeutic strategies.