Longitudinal monitoring of cardiac siderosis using cardiovascular magnetic resonance T2* in patients with thalassemia major on various chelation regimens: a 6-year study.

Cardiovascular magnetic resonance (CMR) and hepatic magnetic resonance imaging (MRI) have become reliable noninvasive tools to monitor iron excess in thalassemia major (TM) patients. However, long-term studies are lacking. We reviewed CMR and hepatic MRI T2* imaging on 54 TM patients who had three or more annual measurements. They were managed on various chelation regimens. Patients were grouped according to their degree of cardiac siderosis: severe (T2*, <10 msec), mild to moderate (T2* = 10-20 msec), and no cardiac siderosis (T2*, >20 msec). We looked at the change in cardiac T2*, liver iron concentration (LIC) and left ventricular ejection fraction (LVEF) at years 3 and 5. In patients with severe cardiac siderosis, cardiac T2* (mean ± SD) improved from 6.9 ± 1.6 at baseline to 13.6 ± 10.0 by year 5, mean ΔT2* = 6.7 (P = 0.04). Change in cardiac T2* at year 3 was not significant in the severe group. Patients with mild to moderate cardiac siderosis had mean cardiac T2* of 14.6 ± 2.9 at baseline which improved to 26.3 ± 9.5 by year 3, mean ΔT2* = 1.7 (P = 0.01). At baseline, median LICs (mg/g dry weight) in patients with severe, mild-moderate, and no cardiac siderosis were 3.6, 2.8, and 3.3, whereas LVEFs (mean ± SD) (%) were 56.3 ± 10.1, 60 ± 5, and 66 ± 7.6, respectively. No significant correlation was noted between Δ cardiac T2* and Δ LIC, Δ cardiac T2*, and Δ LVEF at years 3 and 5. Throughout the observation period, patients with no cardiac siderosis maintained their cardiac T2* above 20 msec. The majority of patients with cardiac siderosis improve cardiac T2* over time with optimal chelation.

Toward optimizing the use of deferasirox: potential benefits of combined use with deferoxamine.

Patients with ß-thalassemia require iron chelation therapy to protect against progressive iron overload and non-transferrin-bound iron. Some patients fail to respond adequately to deferoxamine and deferasirox monotherapy while others have side effects which limit their use of these drugs. Since combining deferiprone and deferoxamine has an additive effect, placing all patients into net negative iron balance, we investigated the possibility that combining deferasirox and deferoxamine would lead to similar results. We conducted 34-day metabolic iron balance studies in six patients in whom the relative effectiveness of deferasirox (30 mg/kg/day) and deferoxamine (40 mg/kg/day) was compared, alone and in combination. Patients consumed fixed low-iron diets; daily urinary and stool iron excretion were determined by atomic absorption. Red blood cell transfusions were given prior to each drug treatment to minimize the effects of ineffective erythropoiesis. Serial safety measures, hematologic parameters, serum chemistries, ferritin levels and urinalyses were determined. All patients were in negative iron balance when treated with deferoxamine alone while four of six patients remained in positive balance when deferasirox monotherapy was evaluated. Daily use of both drugs had a synergistic effect in two patients and an additive effect in three others. Five of six patients would be in negative iron balance if they used the combination of drugs just 3 days a week. No significant or drug-related changes were observed in the blood work-ups or urinalyses performed. We conclude that supplementing the daily use of deferasirox with 2 - 3 days of deferoxamine therapy would place all patients into net negative iron balance thereby providing a convenient way to tailor chelation therapy to the individual needs of each patient.