Changes in MRI-Estimated Cardiac and Hepatic Iron Load in β-Thalassemia Patients Treated with Deferasirox at a Single Institution

Chronic transfusions have dramatically improved the life expectancy of patients with β-thalassemia, but leads to severe iron overload. Long-term iron chelation therapy aims both in the prevention and the reversal of iron load and iron toxicity. The available chelators seem to have different profiles of relative heart and liver iron removal. Data on cardiac efficacy of deferasirox (DFX; Exjade^®) are limited. We report results on patients with thalassemia, followed in a single institution, who completed at least 12 months of treatment with deferasirox.

Methods: Fifty five patients (22 males, 33 females; mean age: 27±7.1 years, splenectomised: 5 patients, HCV seropositive: 7 patients) were included in the study. The patients were treated with deferasirox at a mean dose of 27.2±5.2 mg/kg/day (range 15–40 mg/kg/day). Sixty-one pairs of MRI assessments of cardiac and hepatic iron overload by using the T2* technique were performed at a mean time interval of 13.7±2.4 months. Cardiac function parameters, mainly ejection function (EF), were also estimated at the same time.

Results: Mean, SD and range at the time of the first MRI evaluation showed: ferritin: 2520±1584 ng/mL (371–6953 ng/mL), cardiac T2*: 25.3±10.7 ms (3.8–39.2ms), liver T2*: 4.5±4.6 ms (0.57–21.1ms) and ejection fraction: 66.9±4.8 ms (55.5–75.4%). Follow up assessments showed: ferritin: 2375±1743 ng/mL (39–7245 ng/mL), cardiac T2*: 27,1±11.7 ms (2.7–40.8ms), liver T2*: 6.2±6.2 ms (0.5–26.4ms) and ejection fraction: 66.1±4.8 ms (55.8–75.4%). Changes in liver and cardiac T2* were statistically significant (p=0.0004 and 0.008, respectively). Changes of the cardiac T2* values correlated well with the dose of deferasirox, while changes of liver T2* with ferritin changes (r=−0.284, p=0.032, r=−0. 27 and p=0.046, respectively). A statistical significant improvement (p<0.05) in cardiac and hepatic iron load was observed in the subgroup of 22 patients with severe liver iron load (defined as hepatic T2*<1.9 ms). In 18 patients with moderate/severe cardiac iron load (cardiac T2*<20ms), T2* decreased in 5, remained stable in 2 and improved in 11 patients (mean 10.7±5.5 ms vs. 12.1±7.1, p=0.078).[S1]

Conclusions: This observational study shows that treatment with deferasirox improves both hepatic and cardiac iron overload in regularly transfused β-thalassemia patients. Adjustment of the dose is required to enhance iron excretion and achieve better negative iron balance