Deferiprone Versus Sequential Deferiprone-Deferoxamine Treatment in Thalassemia Major: A Five Years Multicenter Randomized Clinical Trial under the Auspices of the Society for the Study of Thalassemia and Hemoglobinopathies (SoSTE).

Three short-term randomised clinical trials suggested not difference of Deferiprone (L1) vs Deferoxamine (DFO) in term of iron overload efficacy in thalassemia major (TM) patients. To assess whether L1 (75mg/Kg) alone was comparable to a sequential treatment using L1 (75mg/Kg) for 4 days and DFO (50mg/Kg) for 3 days, we carried ahead a large long-term randomised clinical trial. One-hundred and forty consecutive patients with TM and serum ferritin between 1,500 and 3,000 ng/ml were randomly assigned to L1 (n°69) or sequential L1-DFO (n°71) and treated for 5 years. The main measure of efficacy was the reduction of serum ferritin levels. Secondary outcomes were liver and heart iron contents assessed by T2* magnetic resonance. After one year-treatment the mean serum feritin reduction was −105 ± 90.4 in L1 and −409 ± 64.2 in sequential L1-DFO treatment (p <0.01), respectively. The greater mean serum ferritin reduction of sequential L1- DFO treatment was also confirmed all over the study (2° year L1 106 ± 713, L1-DFO -321 ± 92 (p <0.01); 3° year L1 137 ± 137, L1-DFO -292 ± 117 (p <0.05); 4° year L1 216 ± 200, L1-DFO-230 ± 170 (p <0.01); 5° year L1 336 ± 244, L1-DFO -598 ± 203 (p <0.01)). After one-year treatment this sequential group showed greater efficacy in term of serum ferritin levels reduction (−409 ± 64.2) in comparison with the DFO alone arm (−232 ± 619) of a previous randomised multicenter clinical trial in which a comparable cohort of patients were studied (p<0.05). Reversible leukocytopenia was shown in 8 (11.5%) L1 and in 7 (9.8%) sequential L1-DFO treated patients. No agranulocythosis was reported on sequential L1-DFO treated patients during the 5 years study. Hypertransaminasemia developed in 13 (18.8%) L1 and in 5 (7%) sequential L1-DFO treated patients. No other major side effects have been reported. Discontinuation of treatment was necessary in 55.6% L1 and in 57.7% sequential L1-DFO treated patients (chi2 0.03, p=0.86). The failures of treatment were less in sequential L1-DFO arm (n°2) in comparison to L1 alone arm (n°8), although this difference not so far reached the statistical significance (chi2 3.4, p=0.06). These findings suggest that sequential L1-DFO treatment in a long-term study is more effective than L1 alone with milder and reversible side effects. Moreover, its efficacy is also higher in comparison with DFO alone at short-term evaluation.

Fig. 1

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VARIATIONS OF THE FERRITIN LEVELS DURING FIVE YEARS TREATMENT BETWEEN THE TWO ARMS OF THE TRIAL

Fig. 1

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VARIATIONS OF THE FERRITIN LEVELS DURING FIVE YEARS TREATMENT BETWEEN THE TWO ARMS OF THE TRIAL

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