Iron overload assessment in β Thalassemia Major – is T2* Magnetic Resonance Imaging the answer?

Dear Editor,

The initial reports in β thalassemia major were published by Lucarelli et al, spanning a decade and performing the procedure in over 1000 patients. An overall 20 years’ thalassemia free survival was reported as 73% (1). It was in the 1980s when the Pesaro group recommended a classification for determining outcome of transplant in patients aged 17 years or less. The variables included: compliance to iron chelation, hepatomegaly and portal fibrosis as documented by liver biopsy. Based on the number of risk factors present, patients were grouped into class I (no risk factors) class II (any one or two risk factors) and class III (all risk factors). According to the categories, the disease free survival was 94%, 77% and 53% for class I, II, III respectively (2). The prognostication grid is very subjective with respect to the presence of liver enlargement and the adequacy of chelation. Moreover, not every patient is willing to undergo an invasive procedure like liver biopsy to determine the extent of portal fibrosis. Allogeneic stem cell transplantation remains to be the only curative treatment option in patients with β thalassemia major (3). The major predictor for a favorable outcome in allogeneic transplant for β thalassemia is the extent of iron overload prior to the procedure (4). T2* Magnetic Resonance Imaging (T2* MRI), is a non-invasive methodology which can be utilized to determine cardiac and liver iron overload (5). For cardiovascular iron overload, T2* MRI is a highly reproducible and sensitive technique. A study done from our center by Alvi N et al., classified 70% of the patients with Thalassemia major as NYHA (New York Heart Association) class II at presentation using this technique. T2* of <20 milliseconds was seen in 62.6% while 47% showed a value of 10 milliseconds or less. There was no correlation of serum ferritin with the value of T2* MRI (p value: 0.464) (6). A recent cross sectional study on 162 subjects with β thalassemia major was done to assess cardiac and liver iron overload simultaneously. Approximately 85% of the subjects had normal cardiac iron stores. However, 70.4% had severe liver iron overload. There was a weak correlation (r=0.28) between cardiac iron stores and serum ferritin levels. The liver iron concentration and serum ferritin showed a considerably more significant correlation (r=0.37) (7). As compared to several other studies, this study also demonstrated that liver siderosis precedes cardiac iron overload. T2* MRI of liver is a non-invasive modality in identifying the degree of iron deposition. Hamidieh AA et al. (8) has used T2* MRI of cardiac and liver in post-transplant patients with β thalassemia major. The pre and post-transplant values were compared and the technique proved to be beneficial in monitoring patients post-procedure. In summary, liver pathologies and inflammatory conditions falsely increase serum ferritin levels, making it an unreliable predictor of liver iron concentration. The gold standard is liver biopsy but it is an invasive procedure and cannot detect cardiac iron status (9). T2* MRI of cardiac and liver used in combination, is a non-invasive, reproducible diagnostic modality for prognostication of iron overload in patients with β thalassemia prior to undergoing allogeneic stem cell transplant. The previous classification requiring liver biopsy can be altered to utilize this technique as a replacement. Moreover, if performed in combination with cardiac magnetic resonance, the assessment of liver and cardiac iron can be done simultaneously.