MRI guided iron assessment and oral chelator use improve iron status in thalassemia major patients

Abstract

Oral iron chelators and magnetic resonance imaging (MRI) assessment of heart and liver iron burden have become widely available since the mid 2000s, allowing for improved patient compliance with chelation and noninvasive monitoring of iron levels for titration of therapy. We evaluated the impact of these changes in our center for patients with thalassemia major and transfusional iron overload. This single center, retrospective observational study covered the period from 2005 through 2012. Liver iron content (LIC) was estimated both by a T2* method and by R2 (Ferriscan® ) technique. Cardiac iron was assessed as cT2*. Forty-two patients (55% male) with transfused thalassemia and at least two MRIs were included (median age at first MRI, 17.5 y). Over a mean follow-up period of 5.2 ± 1.9 y, 190 MRIs were performed (median 4.5 per patient). Comparing baseline to last MRI, 63% of patients remained within target ranges for cT2* and LIC, and 13% improved from high values to the target range. Both the median LIC and cT2* (cR2* = 1000/cT2*) status improved over time: LIC 7.3 to 4.5 mg/g dry weight, P = 0.0004; cR2* 33.4 to 28.3 Hz, P = 0.01. Individual responses varied widely. Two patients died of heart failure during the study period. Annual MRI iron assessments and availability of oral chelators both facilitate changes in chelation dose and strategies to optimize care.

Figure 1

a: Changes in chelator dosage regimen (without change in chelator). “Other Reason” included research studies which defined a dose and one subject who modified his own doses (without change in prescription) when ferritin levels were very close to 500 ng/mL. b: Changes in chelator regimen only. “Changes” could include i) changes in monotherapy, ii) change to multiple chelators, and iii) drug holidays for toxicity or for low ferritin (DFX).

Figure 2

Box-and-Whisker Plots. a: Cardiac iron status from first to last MRI for each subject. Reciprocal cR2* and cT2* are on left and right Y axes, respectively. Although clinicians have become accustomed to using cT2* clinically, it is reciprocally related to iron concentration, and so gives a highly nonlinear response. b: Liver iron status estimated by R2 (Ferriscan®) and T2*. In both panels, the boxes represent IQR; the median is shown by the horizontal line. The error bars represent 95 percentile, and outliers are shown. P values are by Wilcoxon signed-rank test.

Figure 3

Bland–Altman Plot comparing LIC assessment by T2* and Ferriscan methods: as described in the Results section, Ferriscan is assigned as the “standard” method. Horizontal lines represent the mean bias and 95% confidence interval for the difference between ferriscan and T2*. Note the positive bias of T2* at low LIC and negative bias of T2* at very high LIC.