Management of Oral Iron Chelator Deferasirox for Transfusion-Dependent Patients with Hematological Disorders: 2-year Experience at a Single Institution in Japan
- 1
- 2
- 3
- 4
- 5
- 6
- 7
Abstract
Introduction: Deferasirox is an oral iron chelator, approved worldwide for the treatment of chronic iron overload due to transfusion. Deferasirox was permitted two years ago in Japan, but there is little known regarding its efficacy and tolerability in clinical practice. Methods: We conducted a retrospective study of 18 patients with transfusion-dependent anemias treated by deferasirox at our institution. The starting dose was individualized and ranged from 6.4 to 26.3 mg/kg/day. Routine clinical laboratory data were followed, and serum ferritin was assessed every 4 weeks. Results: The mean serum ferritin level of 18 patients at the time of deferasirox induction was 3162 ng/ml. Ten of 18 patients could sustain deferasirox treatment for at least 6 months, at an average maintenance dose of 10.8 mg/kg/day. Serum ferritin reduction was observed in 4 patients, at doses less than 20 mg/kg/day. Eighty-nine percent of the patients had adverse events, and 13 of them in all ultimately discontinued. Myelodysplastic syndrome (MDS) patients showed poor tolerability. Severe infections of grade 3 or more were documented in 6 patients, and 2 of them were fatal. Conclusions: The potential for beneficial iron chelation of deferasirox at less than the recommended 20 mg/kg dose was demonstrated. On the contrary, poor tolerability was documented, with adverse events such as severe infections, especially in MDS patients. Although it was not clearly demonstrated that deferasirox was responsible for impaired immunity, careful watching is required to administrate deferasirox.
- Andrews NC, “Disorders of iron metabolism,” N Engl J Med, Vol. 341, December 1999, pp. 1986-1995.
- Kushner JP, Porter JP, and Olivieri NF, “Secondary iron overload,” Hematology Am Soc Hematol Educ Program, 2001, pp. 47-61.
- Takatoku M, Uchiyama T, Okamoto S, Kanakura Y, Sawada K, Tomonaga M, Nakao S, Nakahata T, Harada M, Murate T, and Ozawa K, and Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes, “Retrospective nationwide survey of Japanese patients with transfusion-dependent MDS and aplastic anemia highlights the negative impact of iron overload on morbidity/mortality,” Eur J Haematol, Jun, 2007, Vol. 7, pp. 487-94.
- Shander A and Sazama K, “Clinical consequences of iron overload from chronic red blood cell transfusions, its diagnosis, and its management by chelation therapy,” Transfusion, May 2010, vol 50, pp. 1144-1155.
- Malcovati L, “Impact of transfusion dependency and secondary iron overload on the survival of patients with myelodysplastic syndromes,” Leuk Res, December 2007, Vol. 31, Suppl 3, S2-6.
- Oliva EN, Ronco F, Marino A, Alati C, Praticò G and Nobile F, “Iron chelation therapy associated with improvement of hematopoiesis in transfusion-dependent patients,” Transfusion, July 2010, vol 50, pp. 1568-1570.
- Giardina PJ and Grady RW, “Chelation therapy in beta-thalassemia: the benefits and limitations of desferrioxamine,” Semin Hematol, October 1995, Vol. 32, pp. 304-312.
- Gabutti V and Piga A, “Results of long-term iron-chelating therapy,”Acta Haematol, 1996, Vol. 95, pp. 26-36.
- Cappellini MD, Cohen A, Piga A, Bejaoui M, Perrotta S, Agaoglu L, Aydinok Y, Kattamis A, Kilinc Y, Porter J, Capra M, Galanello R, Fattoum S, Drelichman G, Magnano C, Verissimo M, Athanassiou-Metaxa M, Giardina P, Kourakli-Symeonidis A, Janka-Schaub G, Coates T, Vermylen C, Olivieri N, Thuret I, Opitz H, Ressayre-Djaffer C, Marks P and Alberti D, “A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia,” Blood, May 2006, Vol. 107, pp. 3455-3462.
- Porter J, Galanello R, Saglio G, Neufeld EJ, Vichinsky E, Cappellini MD, Olivieri N, Piga A, Cunningham MJ, Soulières D, Gattermann N, Tchernia G, Maertens J, Giardina P, Kwiatkowski J, Quarta G, Jeng M, Forni GL, Stadler M, Cario H, Debusscher L, Della Porta M, Cazzola M, Greenberg P, Alimena G, Rabault B, Gathmann I, Ford JM, Alberti D and Rose C, “Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study,” Eur J