Defining serum ferritin thresholds to predict clinically relevant liver iron concentrations for guiding deferasirox therapy when MRI is unavailable in patients with non‐transfusion‐dependent thalassaemia

Abstract

SummaryLiver iron concentration (LIC) assessment by magnetic resonance imaging (MRI) remains the gold standard to diagnose iron overload and guide iron chelation therapy in patients with non‐transfusion‐dependent thalassaemia (NTDT). However, limited access to MRI technology and expertise worldwide makes it practical to also use serum ferritin assessments. The THALASSA (assessment of Exjade® in non‐transfusion‐dependent THALASSemiA patients) study assessed the efficacy and safety of deferasirox in iron‐overloaded NTDT patients and provided a large data set to allow exploration of the relationship between LIC and serum ferritin. Using data from screened patients and those treated with deferasirox for up to 2 years, we identified clinically relevant serum ferritin thresholds (for when MRI is unavailable) for the initiation of chelation therapy (>800 μg/l), as well as thresholds to guide chelator dose interruption (<300 μg/l) and dose escalation (>2000 μg/l). (clinicaltrials.gov identifier: NCT00873041).

HbH Constant Spring disease has lower serum ferritin relative to liver iron concentration (LIC): importance of LIC measurement and potential impact on serum ferritin thresholds for iron chelation

“…In Group 1 subjects, 89% had LIC of ≥5 mg/g dw, of which 25% had corresponding serum ferritin of <500 μg/l (with the lowest serum ferritin being 224 μg/l). A serum ferritin of ≥800 μg/l proposed by Taher et al () had the lowest NPV among our patients with HbHCS for predicting LIC of ≥5 mg/g dw, and might cause delay in initiation of iron chelation in 67·7% (or 1‐NPV) of the patients if this serum ferritin threshold was adopted when MRI was unavailable. This risk of delay in iron chelation therapy was higher than the 43·9% in our deletional HbH disease patients and the 46·4% in NTDT patients reported in the study by Taher et al () (Table ).…”

“…However, due to the cost and limited availability of MRI, serum ferritin is often used as a surrogate marker of liver and body iron load in thalassaemia patients. Taher et al () recently reported good correlation between serum ferritin and LIC in a large NTDT population comprising HbE/β thalassaemia, β thalassaemia intermedia and HbH disease, and advocated a serum ferritin threshold of 800 μg/l for initiation of chelation therapy when MRI assessment of LIC was unavailable. This threshold had the highest overall accuracy in their cohort of patients for predicting LIC of ≥5 mg/g dry weight (dw), with positive and negative predictive values (NPV) of 91·7% and 53·6%, respectively (Taher et al , ).…”

Iron overload in patients with rare hereditary hemolytic anemia: Evidence‐based suggestion on whom and how to screen

“…We recommend that MRI LIC measurement should be performed in all patients. Recently, in a study in non‐transfusion dependent thalassemia patients, a ferritin cut‐off of 800 ng/mL was demonstrated to have the best predictive value for iron overload (defined as LIC ≥ 5 mg/g) when MRI is unavailable 2. Both in our rare HHA sample and in the reference group, the sensitivity of a cut‐off of 800 ng/mL for LIC ≥ 7 mg/g remained poor.…”

Effect of Iron Chelation Therapy on Glucose Metabolism in Non-Transfusion-Dependent Thalassaemia

“…The LIC of ≥5 mg Fe/g dry weight indicates the status of iron overload requiring appropriate iron chelation [18]. In the THALASSA (Assessment of Exjade® in Non-Transfusion-Dependent Thalassemia Patients) study by Taher et al [19], a serum ferritin level of ≥800 ng/ml had the highest positive predictive value of 91.7% for LIC ≥5 mg Fe/g dry weight. However, the normal levels of serum ferritin are 12-300 ng/ml for males and 12-150 ng/ml for females.…”