Summary
Deferasirox is a once‐daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open‐label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non‐progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11·4%) and deferoxamine (11·1%) were similar. Over 1 year, similar dose‐dependent LIC reductions were observed with deferasirox and deferoxamine. Once‐daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease.
Purpose
We aimed to determine the agreement between quantitative susceptibility mapping (QSM)-based biomagnetic liver susceptometry (BLS) and confounder-corrected R2* mapping with superconducting quantum interference device (SQUID)-based biomagnetic liver susceptometry in patients with liver iron overload.
Methods
Data were acquired from two healthy controls and 22 patients undergoing MRI and SQUID-BLS as part of routine monitoring for iron overload. MR imaging was performed on a 3T system using a 3D multi-echo, gradient-echo acquisition. Both magnetic susceptibility and R2* of the liver were estimated from this acquisition. Linear regression was used to compare estimates of QSM-BLS and R2* to SQUID-BLS.
Results
Both QSM-BLS and confounder-corrected R2* were sensitive to the presence of iron in the liver. Linear regression between QSM-BLS and SQUID-BLS demonstrated the following relationship: QSM-BLS = (−0.22 ± 0.11) + (0.49 ± 0.05) · SQUID-BLS with r2 = 0.88. The coefficient of determination between liver R2* and SQUID-BLS was also r2 = 0.88.
Conclusion
We determined a strong correlation between both QSM-BLS and confounder-corrected R2* to SQUID-BLS. This study demonstrates the feasibility of QSM-BLS and confounder-corrected R2* for assessing liver iron overload, particularly when SQUID systems are not accessible.
Serum ferritin (SF) and liver iron concentration (LIC), as measured by SQUID biosusceptometry, were assessed in a convenience sample of transfusion independent thalassemia patients (nTx-Thal, n=26), regularly transfused thalassemia (Tx-Thal, n=89), or sickle cell patients (SCD, n=45) to investigate the severity of iron overload and the relationship between SF and LIC in nTx-Thal compared to SCD and Tx-Thal. SF correlated with LIC (RS=0.53, P<0.001), but was found to be a poor predictor for LIC. SF was significantly lower (P<0.001) in nTx-Thal patients than in other groups, despite similar LIC values. The SF-to-LIC ratio was significantly lower in nTx-Thal compared to Tx-Thal and SCD patients (median of 0.32, 0.87, and 1.2, respectively: P<0.001). Due to underestimation of LIC by ferritin levels, chelation treatment may be delayed or misdirected in patients with thalassemia intermedia.
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