This report updates the combined experience of four centres involved in the long-term treatment of transfusional iron overload in 84 patients with the oral iron chelator deferiprone (L1) over 167 patient-years. The source of L1 was variable, including two university research laboratories and three pharmaceutical firms. Compliance was rated as excellent in 48%, intermediate in 36%, and poor in 16% of patients. On a mean L1 dose of 73-81 mg/kg/d, urinary iron excretion was stable, at around 0.5 mg/kg/d, with no indication of a diminishing response with time. Serum ferritin showed a very steady decrease with time from an initial mean +/- 1 SD of 4207 +/- 3118 to 1779 +/- 1154 micrograms/l after 48 months (P < 0.001). 17 patients abandoned L1 therapy. Major complications of L1 requiring permanent discontinuation of treatment included agranulocytosis (three), severe nausea (four), arthritis (two) and persistent liver dysfunction (one). The remaining patients abandoned treatment because of low compliance (three) and conditions unrelated to L1 toxicity (four). Lesser complications permitting continued L1 treatment included transient mild neutropenia (four), zinc deficiency (12), transient increase in liver enzymes (37), moderate nausea (three) and arthropathy (17). There was no treatment-related mortality. Although the complications associated with L1 treatment are significant and require close monitoring, they do not preclude effective long-term therapy in the vast majority of patients. Further well-controlled prospective studies of L1 are required in order to enable proper judgement of its suitability for general long-term clinical use.

Fifty-one transfusion-dependent iron-loaded adult patients (38 with thalassemia major) were treated with the orally active iron chelator deferiprone (1,2 dimethyl-3-hydroxypyrid-4-one, L1) at a dose of 75 mg/kg/d (range, 50 to 79). Twenty patients discontinued the drug and five died after a mean of 18.7 months (range, 4 to 35). Of the 20, 5 had arthropathy, 5 had gastrointestinal symptoms, 4 had a rising serum ferritin, 3 had agranulocytosis or neutropenia, 1 had tachycardia, 1 had renal failure, and 1 went abroad. Twenty-six patients continued deferiprone for a mean of 39.4 months (range, 12 to 49). Among these patients, there was no overall significant change in serum ferritin (initial mean, 2,937 μg/L; range, 980 to 5,970; final mean, 2,323 μg/L; range, 825 to 5,970) or in urine iron excretion (initial mean, 31.2 mg/24 h; range, 16.3 to 58.2; final mean, 32.1 mg/24 h; range, 9.4 to 75.8), implying no overall change in iron stores. When the patients who had received deferiprone for longer than 3 years were considered separately, there was also no significant change in serum ferritin or urinary iron excretion. The initial serum ferritin levels in the 26 patients who continued deferiprone treatment were significantly lower than in those who discontinued the drug (P < .01). The liver iron content in 17 patients who had received deferiprone for 24 to 48 months ranged from 5.9 to 41.2 mg/g dry weight, 50% having levels above 15.0 mg, a level associated with a high risk of cardiac disease due to iron overload. In this study the drug caused fewer side effects and was more effective at maintaining iron status among patients previously well chelated and with lower initial serum ferritin levels.

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Non-transferrin-bound iron (NTBI) in plasma is toxic due to its ability to participate in free radical formation with resultant peroxidation and damage to cell membranes and other biomolecules. NTBI concentration was determined in serum in 12 normal volunteers and in 52 patients with beta-thalassaemia major by a modification of the method described by Singh et al (1990). There was no detectable NTBI in normal individuals. In the patients NTBI values ranged from -1.5 to 9.0 mumol/l (mean +/- SD: 3.6 +/- 2.3). The patients' serum ferritin concentrations ranged from 207 to 11,400 micrograms/l (2674 +/- 2538), total serum iron from 20 to 61 mumol/l (39.5 +/- 9.6) and transferrin saturation from 44 to 110% (84.5 +/- 13.8). The NTBI correlated significantly with serum ferritin (r = 0.467, P < 0.001), total serum iron (r = 0.608, P < 0.001) and transferrin saturation (r = 0.481, P < 0.005). When patients were grouped according to their compliance with desferrioxamine (DFX) therapy, the good compliers had significantly lower NTBI concentrations compared to the poor compliers (poor: 5.4 +/- 1.8 mumol/l v good: 2.7 +/- 1.7 mumol/l, P < 0.001). There was also a significant difference between the level of NTBI and whether or not the patients had complications of iron overload (5.2 +/- 1.7 mumol/l v 2.9 +/- 1.6 mumol/l, P < 0.001). During this study 10 patients were entered into a trial of the oral iron chelator 1,2- dimethyl-3-hydroxypyrid-4-one (L1). Their NTBI values were observed during the first 6 months of the trial and showed a significant fall (paired t-test: P = 0.007). These results suggest that the level of NTBI may prove helpful in assessing the efficiency of chelation in patients with transfusion dependent anaemia and help to predict organ damage.