Introduction of higher doses of deferasirox: better efficacy but not effective iron removal from the heart and increased risks of serious toxicities

Abstract

Only few patients may benefit from the introduction of higher doses of deferasirox. There is a need for introducing more effective prophylactic measures. Safer, more effective and less costly chelation treatments are available using deferiprone, deferoxamine and their combination.

Association between renal iron accumulation and renal interstitial fibrosis in a rat model of chronic kidney disease

“…14 In addition, safety of DFX is reported in patients with CKD undergoing hemodialysis 30 and myelodysplastic syndrome; 31 however, it is noteworthy that side effect of DFX is mild and reversible increases in serum creatinine levels. 31,32 Fanconi syndrome is also reported as a rare complication (complication rate is 0.1-1%) in both adult and pediatric patients treated with DFX. 33 In other words, the effects of DFX on renal function remain controversial.…”

Toward optimizing the use of deferasirox: potential benefits of combined use with deferoxamine

“…43 Moreover, increasing the dose of the drug is problematic as evidence of toxicity has also increased. 47 The efficacy of DFX might also be increased by splitting the dose. Chang et al reported that serum ferritin levels declined by nearly 40% in 11 patients, who were unresponsive to once daily doses of DFX, after treatment for 6 months with twice daily dosing, the total dosage being the same.…”

Estimation of liver T*2 in transfusion‐related iron overload in patients with weighted least squares T*2 IDEAL

“…Total 37 patients (23 males, 14 females), ages 3 weeks to 34 years (mean age 15, standard deviation 7), were included. Underlying pathologies for the subjects were beta thalassemia ( 13), leukemia/lymphoma (6), Diamond–Blackfan anemia (4), aplastic anemia (4), sickle cell anemia (3), red cell aplasia (2), and one case each of hemophagocytic syndrome, pyruvate kinase deficiency associated anemia, Ewing sarcoma, neonatal hemochromatosis, and Fanconi anemia. All studies were performed in a Health Insurance Portability and Accountability Act (HIPPA) ‐compliant fashion on a GE 1.5T HDx scanner (GE Healthcare, Waukesha, WI).…”

“…Without accurate assessment of degree of iron overload in each organ, including the liver, clinicians may increase doses of chelation when this is not truly indicated ( 1, 2). These higher doses may also lead to increased toxicity (3). Thus, accurate quantification of iron deposition in various organs is essential for therapeutic decision‐making.…”

“…However, the clinical use of MRI for this purpose is hampered by several issues: ( 1) postprocessing to calculate T 2 * in many clinical settings is not fully automated, (2) transfusion‐related iron overload may result in markedly elevated hepatic iron concentration, and hence all but the shortest echoes contain very little signal and are dominated by noise, making accurate quantification challenging, (3) hepatic iron deposition can have spatial heterogeneity, and (4) the presence of hepatic steatosis can potentially confound T 2 * measurements. To address some of these issues, we have previously demonstrated that R 2 * mapping can be achieved simultaneously with water–fat separation using a multiple‐echo acquisition and a T 2 * Iterative Decomposition of water and fat with Echo Asymmetry and Least‐squares estimation (IDEAL) reconstruction algorithm (21).…”