Efficient Iron Chelation Resulting in Improved Myocardial Performance with Combined Desferrioxamine and Deferiprone in Beta Thalassemia Major Patients.
Authors: Pathare Anil V. , Daar Shahina , Kindi Salam Al , Dennison J. David 
Published: October 2019

Background: Iron overload is the main cause of morbidity and mortality especially from heart failure in patients with beta thalassemia major [TM]. Successful iron chelation is thus essential for the optimal management of TM. Although desferrioxamine [DFX] has been the major iron-chelating treatment of transfusional iron overload, compliance is a major hindrance. The availability of oral iron chelation with deferiprone [L1] since 1987 was welcome but showed poor efficacy when used alone as compared to DFX.

Aim: To compare DFX and prospective combined therapy with DFX and L1 in beta thalassemia major patients with iron overload.

Methods: We studied 69 patients with beta thalassemia major (Mean age ± SD, 15.02± 5.8; Range 4–28 years) attending the Day Care unit for regular transfusional support. They received packed red cells every 3–4 weeks to maintain pre-transfusion hemoglobin concentration above 9 g/dl. They were receiving DFX at a daily dose of 40mg/kg/day by subcutaneous infusion for 8–10 hrs on 4–5 nights each week for past several years. However, owing to various reasons, they developed considerable transfusional iron overload. These patients were enrolled prospectively to receive additional therapy with oral iron chelator L1 at 75 mg/kg body weight in three divided doses with food after informed consent and also continued to receive treatment with DFX as per the above dosage.

Results: Of the 69 patients, 6 developed severe GI upset, 2 developed persistently raised liver enzymes, 2 died [sepsis], two underwent bone marrow transplantation and 2 developed agranulocytosis and so did not continue in the study. In the remaining 55 evaluable patients, [3–48 months on combination therapy; mean(±SD) 22±12 months] the mean serum ferritin(±SD) fell dramatically from 3088(±1299) [DFX alone] to 2051(±935)ng/ml [DFX+L1; p<0.001], with the mean of lowest serum ferritin being 1731(±828) ng/ml in this group. Interestingly, there was also a significant improvement in the Ejection fraction [p<0.004]and Fractional shortening[p<0.0436] in these patients.

Sustained successful iron chelation on combination therapy

Ferritin pretherapy[DFX] 6mths[DXF+L1] 12 mths [DXF+L1] 18mths [DXF+L1] 24mths [DXF+L1] 36mths [DXF+L1] 48 mths [DXF+L1] No of Patients n=55 n=54 n=42 n=32 n=24 n=12 n=7 Mean± SD 3088±1299 2530±1221 2495±1175 2433±1154 2165±889 1686±917 997±318 Range-Max 7534 6070 5559 5126 4130 3172 1471 Range-Min 1072 599 776 408 712 473 559 Students t test[DFX v/s DFX+L1] p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001

Improved myocardial performance on combination therapy

Pretherapy [DFX] Combination Therapy [DFX+L1] p value Ejection Fraction [%] 69.04±5.182 72.99±5.54 p<0.0004 Fractional Shortening [%] 32.19±4.32 34.89±5.4 p<0.0436

Summary/Conclusion: The study emphasizes that beta thalassemia major patients with transfusional iron overload can be successfully treated with a combination of DFX and L1. The results also demonstrate significant statistical improvement as early as 6 months of combination therapy. Furthermore, this improvement was sustained leading to a progressive fall in the mean serum ferritin. Lastly, the study also demonstrates significant improvement in echocardiographic parameters of myocardial performance in these patients receiving combination therapy.