Deferasirox Therapy in Children With Fanconi Aplastic Anemia

Abstract

Thirty-nine children with Fanconi aplastic anemia (FAA) have been followed up in our center between January 2008 and November 2010. Eight of these children (20%) with a transfusional iron overload had been undergoing deferasirox treatment during the study period. In the English literature, transfusional iron overload and the use of an iron chelator in children with FAA has not yet been evaluated. Here, we have presented the effectivity and tolerability of deferasirox in children with FAA and a transfusional iron overload. Before the deferasirox treatment, the mean serum ferritin level was 3377 ± 2200 ng/mL. After a mean 13.6-month treatment duration, the mean ferritin level decreased to 2274 ± 1300 ng/mL (P<0.05). In our series, 3 patients had renal and 3 had hepatic toxicity during the treatment. Two patients had peliosis hepatis and 2 had congenital renal abnormalities before the treatment. There may be differences in the side-effect profiles of deferasirox treatment in patients with FAA. In our series, despite the low number of cases, nephrotoxicity and hepatotoxicity were common side effects instead of gastrointestinal disturbances reported in other studies. Deferasirox is an oral, easily applicable, and effective iron chelator; baseline hepatotoxicity and nephrotoxicity may increase the development of toxic side effects in children with FAA. Patients with FAA receiving deferasirox treatment should be followed up closely for these side effects.

Bone marrow cell transcripts from Fanconi anaemia patients reveal in vivo alterations in mitochondrial, redox and DNA repair pathways

“…Systematic studies of in vivo iron metabolism in patients with FA are currently lacking to the best of our knowledge; nevertheless, some recent reports found iron overload and excess serum ferritin levels. Elucidating iron metabolism in patients with FA requires investigations that might shed light in FA pathogenesis, while suggesting the prospect use of iron chelators in FA clinical management . Interestingly, transcripts for metallothioneins (2A and 3) were up‐regulated (Table ), consistently with the established link between oxidative stress and increase in metallothionein expression .…”

“…It has been reported that FA cells display hypersensitivity towards iron . Systematic studies of in vivo iron metabolism in patients with FA are currently lacking to the best of our knowledge; nevertheless, some recent reports found iron overload and excess serum ferritin levels. Elucidating iron metabolism in patients with FA requires investigations that might shed light in FA pathogenesis, while suggesting the prospect use of iron chelators in FA clinical management .…”

Deferasirox nephrotoxicity—the knowns and unknowns

“…37,38,40,[60][61][62][63][64][65][66][67][68][69][70][71][72] Among 72 patients with β-thalassaemia major or intermedia who were treated with 20 mg/kg per day of deferasirox for 17 months, an increase in sCr levels >33% above baseline was observed in 46 (64%) patients and deferasirox was discontinued in seven (11%) patients. 60 Serum cystatin C levels are a more sensitive indicator of changes in GFR than are sCr levels.…”

Safety and efficacy of deferasirox in the management of transfusion-dependent patients with myelodysplastic syndrome and aplastic anaemia: a perspective review

“…Proteinuria, which may be intermittent, has been reported in about 18% of patients, and may be more common in children with Fanconi anaemia, with a single small study of this population reporting an unexpectedly high proportion of these children developing proteinuria [Tunc et al 2012]. It is recommended that urinary protein be monitored in patients who develop renal impairment.…”