Iron chelation therapy for patients with sickle cell disease and iron overload

Abstract

A 21-year-old male with sickle cell disease (SCD) presented with severe pallor. He had received a total of 100 red blood cell (RBC) units in his lifetime, had a mean serum ferritin level of 3133 ng/ml, and liver iron concentration (LIC) of 12 mg Fe/g dry weight (dw). He was started on subcutaneous deferoxamine (DFO) infusions at a dose of 56 mg/kg/d, five days a week (equivalent to 40 mg/kg/d, seven days a week) and continued to receive 8-10 RBC units/year as treatment for pain. During the first six months of chelation therapy, his serum ferritin levels fell by around 50% of the pretreatment value, but then started to increase back up to the baseline values. The patient was noncompliant with DFO therapy. He experienced pain at the site of injection, could not sleep and was concerned about carrying a pump and not being accepted by his peers. He dropped out of college and abstained from all social activities. He was referred to a psychologist; however, this failed to improve compliance and he opted to stop DFO therapy altogether.The role of iron chelation therapy has long been acknowledged in the management of iron overload in patients receiving blood transfusion therapy; however, data specific to the treatment of patients with SCD are limited. DFO (Desferal 1 ; Novartis Pharma AG, Basel, Switzerland) was the first iron chelator to be licensed, more than 40 years ago, for chronic iron overload as a result of transfusion-dependent anemia and remains the current reference standard iron chelator. The efficacy and safety of DFO is well established in patients with b-thalassemia major [1-3]; however, clinical evaluation in SCD-specific populations is limited. Early small-scale studies of transfused patients with SCD showed that DFO was able to increase urinary iron excretion [4,5] and intensive chelation regimens in heavily iron-overloaded patients with SCD showed acceptable efficacy and safety [6][7][8]. In these small-scale studies, there were no reported incidences of impaired hearing or visual acuity, toxicities that have been noted in patients with b-thalassemia major and other rare anemias when doses are inappropriately high for the level of iron overload [9]. However, careful regulation of dosage and regular audio-visual monitoring is still advised. Increased zinc excretion demonstrated at very high DFO doses (180 mg/kg) [8] may lead to extreme zinc deficiency in patients with SCD who may already have decreased plasma zinc levels [10]. The verification of possible adverse events specific to patients with SCD most certainly requires further study.The major limitation of DFO is the requirement for frequent, slow parenteral administration, which can be painful and inconvenient. Compliance has a noticeable impact on a patient's response to therapy and can have serious consequences, as described in this case. In patients with b-thalassemia major, the demands of DFO therapy have been shown to have a negative impact on quality of life and mental health [11]. The impact of infusions may be greatest for adolescents and y...

How I treat transfusional iron overload

“…Serum ferritin, LIC, and cardiac T2* MRI and cardiac, hepatic, renal, and endocrine (thyroid, parathyroid, pancreatic, gonadal, and pituitary) function also need to be tested. 2,91,92 Potential for pregnancy and the growth and development in children are also assessed. 2 The overall prognosis in the chronic anemias other than TM must be assessed.…”

“…36,91,92 A LIC Ͼ 15 mg/g dry weight, serum ferritin Ͼ 2500 g/L or cardiac T2* MRI Ͻ 20 ms indicate inadequate chelation. If cardiac iron overload is present (T2* Ͻ 20 ms), cardiac iron removal becomes the primary goal of therapy ( Table 4).…”

Chelation Therapy for Iron Overload

“…2 Iron overload is an important cause of morbidity and mortality of these patients, especially those who are treated with monthly chronic red cell transfusions for sickle-cell complications like stroke. 8,12 …”

“…2,4,5,7,11,13,14 Most often, it is due to the required regimen and the high cost of the drug that causes inconsistent patient adherence to the dosing. 2–5,8,11–14,17 …”

“…Untreated, iron overload can cause deleterious effects on many organs, such as the liver, and the cardiac and endocrine systems. 1–8 The effects of iron overload are visible after damage has been done, where patients have liver dysfunction, cardiomyopathy, or diabetes. 4,6 Chelation therapy provides a viable method of treating iron overload and minimizing the adverse effects associated with iron overload.…”