Iron overload and desferrioxamine chelation therapy in β-thalassemia intermedia

Abstract

This study on serum ferritin levels in urinary iron excretion after 12h subcutaneous infusion of desferrioxamine in 10 thalassemia intermedia patients shows that even nontransfusion-dependent patients may have positive iron balance resulting in iron overload from 5 years of age. However, the iron overload found in these patients appears to be much lower than in age matched patients with transfusion-dependent thalassemia major. Iron overload increases with advancing age, as shown by increasing serum ferritin levels and desferrioxamine-induced urinary iron elimination. After a six month trial of 12h continuous subcutaneous desferrioxamine administration there was a significant decline in serum ferritin levels. From this study it seems that iron chelation is indicated in thalassemia intermedia patients over 5 years of age in order to prevent iron accumulation. However, the appropriate treatment schedule should be tailored to the individual needs of each patients, established by close monitoring of serum ferritin levels and desferrioxamine-induced urinary iron elimination.

Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study

“…These data provide the largest set of efficacy and safety data for iron-chelation therapy in NTDT patients to date, confirming preliminary findings in small studies and case reports. 4,[8][9][10][11][12][13][14] Despite no or only sporadic transfusions in these NTDT patients, high baseline LIC and serum ferritin levels confirm significant iron burden requiring iron chelation. In patients receiving placebo treatment, LIC and serum ferritin increased by 0.38 mg Fe/g dw (95% CI, Ϫ0.59 to 1.34) and 115 ng/mL, respectively, over 1 year; only 6 (10.7%) patients required transfusions in this group during this time.…”

“…2 Iron overload in NTDT patients results primarily from increased intestinal iron absorption caused by ineffective erythropoiesis 3 and may develop as early as 5 years of age. 4 Iron overload usually becomes clinically relevant after 10 years, 5 making iron loads in NTDT patients in their 30s and 40s comparable to those in transfusion-dependent ␤-thalassemia patients. 3 For example, in a previous study of ␤-thalassemia major patients (mean age, 17 years), LIC was 11.1 mg Fe/g dry weight (dw), although this may reflect prior suboptimal chelation therapy.…”

“…Data on iron chelation in NTDT patients are currently restricted to small, uncontrolled studies and case reports. 4,[8][9][10][11][12][13][14] Deferasirox (Novartis Pharmaceuticals) is a once-daily oral iron chelator with demonstrated efficacy and a well-characterized safety profile in patients with chronically transfused anemias. [15][16][17][18][19][20] Given the different pathophysiology of iron metabolism and the slower iron-loading rate in NTDT compared with transfusiondependent ␤-thalassemia patients, it is important to establish the efficacy, safety, and optimal doses of deferasirox in this population.…”

Non-transfusion-dependent thalassemias

“…[92][93][94] A beneficial effect of iron chelation in reducing clinical morbidity risk in patients with NTDT is suggested by observational studies and further long-term studies in this direction are needed.…”

Ineffective erythropoiesis in β-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin

“…However, progressive iron overload still occurs due to increased gastrointestinal (GI) iron absorption. [3][4][5] Studies in thalassemic patients showed that the rate of iron uptake from the GI tract is approximately 3 to 4 times greater than normal. 6 Ferrokinetic studies revealed that 75% to 90% of the iron in donor serum, labeled with 59 Fe and injected into healthy subjects, appeared in circulating red cells within 7 to 10 days.…”