Effect of deferasirox on serum ferritin level in children with thalassemia major: impact of transfusional iron load

Authors

  • Santosh K. Shukla Department of Pediatrics, Motilal Nehru Medical College, Prayagraj, Uttar Pradesh, India
  • Anubha Shrivastava Department of Pediatrics, Motilal Nehru Medical College, Prayagraj, Uttar Pradesh, India
  • Prakash C. Mishra Department of Pediatrics, Motilal Nehru Medical College, Prayagraj, Uttar Pradesh, India

DOI:

https://doi.org/10.18203/2349-3291.ijcp20193729

Keywords:

Deferasirox, Iron load, Serum ferritin, Thalassemia, Transfusional

Abstract

Background: Ongoing transfusional iron load (TIL) is an important determinant while deciding starting and subsequent dose adjustment of deferasirox during course of chelation therapy. So present study aims to find out effect of different dosing of deferasirox over the serum ferritin level in children with thalassemia major with impact of rate of transfusional iron load.

Methods: This one year observational study was carried out in 35 transfusion dependent β-thalassemic patients aged 2-18 years. Patients with baseline serum ferritin 1000-1500ng/ml and/or receiving TIL 0.2-0.3mg/kg/day were started 20mg/kg/day deferasirox and patients with ferritin>1500ng/ml and/or having TIL > 0.3mg/kg/day were started 30mg/kg/day deferasirox. Serum ferritin was repeated in every three months. Dose adjustments were performed on serum ferritin trends in steps of 5-10mg/kg /day to maximum 40mg/kg/day. Evaluation of relationship between dose adjustment, percentage of reduction in serum ferritin and TIL was done.

Results: Group-1 patients(42.8%) had TIL 0.2 to 0.3mg/kg/day whereas Group-2(37.1%) and Group-3(20%) children had TIL >0.3-0.4mg/kg/day and >0.4 mg/kg/day respectively. Starting dose of deferasirox in 25.7% patients was 20mg/kg/day and in rest were 30mg/kg/day. Average dose of deferasirox in group-1 was significantly lower as compared to group-2 and group-3 patients ( p< 0.05). Significant decline in mean serum ferritin was observed in all three groups (p < 0.05). There was a significant positive correlation between TIL and average drug dose prescribed (r=0.5411and p=0.0007) but negative insignificant correlation was observed with percentage of reduction in serum ferritin(r=0.0027and p=0.98).

Conclusions: Deferasirox 30mg/kg/day significantly reduces serum ferritin and is well tolerated in majority of patients having TIL 0.3-0.4mg/kg/day where as 20mg/kg/day is required in patients having low transfusional iron intake.

References

Porter JB. Practical management of iron overload. British J Haematol. 2001;115:239-52.

Porter J, Viprakasit V. Iron overload and chelation. In: Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V. Guidelines for the management of transfusion dependent thalassemia (TDT). 3rdedition. Thalassemia International Federation; 2014:42-97.

Porter JB, Elalfy M, Taher A, Aydinok Y, Lee SH, et al. Limitation of serum ferritin to predict liver iron concentration responses to deferasirox therapy in patients with transfusion-dependent thalassemia. Europ J Haematol. 2017 Mar;98(3):280-8.

Cohen AR, Glimm E, Porter JB. Effect of transfusional iron intake on response to chelation therapy in β-thalassemia major. Blood. 2008 Jan 15;111(2):583-7.

Cappellini MD, Cohen A, Piga A, Bejaoui M, Perrotta S, Agaoglu L, et al. A phase 3 study of dererasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia. Blood. 2006;107(9):3455-62.

Taher A, Cappellini MD,Vichinsky E, Galanello R, Piga A, Lawniczek T, et al. Efficacy and safety of deferasirox doses of > 30 mg/kg per d in patients with transfusion dependent anemia and iron overload. Br J Haematol. 2009;147(5):752-9.

Trehan A, Sharma N, Das R, Bansal D, Marwaha R.K.; Clinicoinvestigational and Demographic Profile of Children with Thalassemia Major. Indian J Hematol Blood Transfus; 2015 Mar;31(1):121-6.

Shah N. Mishra A, Chauhan D, Vora C, Shah NR. Study on effectiveness of transfusion program in thalassemia major patients receiving multiple transfusions at a transfusion centre in Western India. Asian journal of transfusion science. 2010 Jul;4(2);94-8.

Thakor DR, Desai CK, Kapadia JD, Dikshit RK, Mehariya KM. Efficacy and safety of Deferasirox in Pediatric Patients of Thalassemia at Tertiary Care Teaching Hospital. Ind J Med Pediatr Oncol. 2017;38 (2):102-10.

Kumari V, Upadhyay SK, Gupta V, Piplani KS, Bhatia BD. Growth Retardation and Malnutrition in Children with Thalassemia Major. Indian J. Prev. Soc. Med. 2012;43(2);149-52.

Cappellini MD, Porter J, El-Beshlawy A, Li CK, Seymour JF, Elalfy M, et al. Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias. haematologica. 2010 Apr 1;95(4):557-66.

Porter J, Galanello R, Saglio G, Neufeld EJ, Vichinsky E, Cappellini MD, et al. Relative response of patients with myelodysplastic syndromes and other transfusion‐dependent anaemias to deferasirox (ICL670): a 1‐yr prospective study. Europ J haematol. 2008 Feb;80(2):168-76.

Porter JB, Lin KH, Beris P, Forni GL, Taher A, Habr D, Domokos G, Roubert B, Thein SL, EPIC Study Investigators. Response of iron overload to deferasirox in rare transfusion‐dependent anaemias: equivalent effects on serum ferritin and labile plasma iron for haemolytic or production anaemias. Eur J Haematol. 2011 Oct;87(4):338-48.

Dhamija M, Mahajan A, Kalra M, Virmani A. Deferasirox in Indian children with thalassemia major: 3 years’ experience. Indian J Med Paediatr Oncol. 2013 Jan-Mar; 34(1):16-20.

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Published

2019-08-23

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Original Research Articles