Original Articles
Vol. 13 No. 1 (2021): Mediterranean Journal of Hematology and Infectious Diseases, Volume 13, 2021
https://doi.org/10.4084/MJHID.2021.065

LONG-TERM EFFECTIVENESS, SAFETY, AND TOLERABILITY OF TWICE-DAILY DOSING WITH DEFERASIROX IN CHILDREN WITH TRANSFUSION-DEPENDENT THALASSEMIAS UNRESPONSIVE TO STANDARD ONCE-DAILY DOSING

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Received: August 2, 2021
Accepted: October 2, 2021
Published: October 29, 2021
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deferasirox, Iron chelation, Iron Overload, Thalassemia

Authors

Jassada Buaboonnam
onco008@yahoo.com
a:1:{s:5:"en_US";s:35:"Siriraj Hospital Mahidol University";}, Thailand.
Chayamon Takpradit
Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, Thailand.
Vip Viprakasit
Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, Thailand.
Nattee Narkbunnam
Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, Thailand.
Nassawee Vathana
Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, Thailand.
Kamon Phuakpet
Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, Thailand.
Kleebsabai Sanpakit
Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, Thailand.
Bunchoo Pongtanakul
Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, Thailand.

Background: Patients with transfusion-dependent thalassemia (TDT) risk iron overload and require iron chelation therapy. Salvage therapy is warranted for patients demonstrating poor chelation responses.

Patients and methods: We retrospectively studied the serum-ferritin (SF) and liver-iron-concentration (LIC) outcomes of patients with TDT treated with twice-daily dosing of deferasirox (TDD-DFX) for > 24 months, after failing to respond to once-daily deferasirox (OD-DFX).

Results: We enrolled 22 patients (14 males and 8 females; median age, 9.2 [3–15.5] years). The median erythron transfusion was 216 (206–277) ml/kg/year. The median TDD-DFX treatment period was 30 (24–35) months. Before initiating TDD-DFX, the median SF level was 2,486 (1,562–8,183) ng/ml, while the median LIC was 6.5 (3.2–19) mg/g dry wt. There were 18 responders (81.8%) and 4 nonresponders. The median SF-level change was -724 (-4 916 to 1,490) ng/mL. The median LIC change was -2.14 (-13.7 to 6.8) mg/g dry wt. The 1-year and end-of-study SF levels and LICs were statistically significant (SF, P = 0.006/0.005; and LIC, 0.006/0.005, respectively). There were no treatment interruptions secondary to adverse events. In the follow-up of the TDD-DFX-responder group, 11 of the 18 had a reduced dose, whereas the remaining 7 continued with the same dose.

Conclusions: TDD-DFX appears to be an alternative treatment approach for patients refractory to OD-DFX, with a favorable long-term safety profile. Further studies with larger groups and pharmacogenetic analyses of inadequate responders are warranted to better determine the efficacy and safety profile of TDD-DFX.

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Citations

Crossref
Scopus
Google Scholar
Europe PMC
Fucharoen S, Winichagoon P. Thalassemia in SouthEast Asia: problems and strategy for prevention and control. Southeast Asian J Trop Med Public Health. 1992;23:647-55
Cappellini MD, Bejaoui M, Agaoglu L, et al. Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up. Blood. 2011;118:884-93. doi:10.1182/blood-2010-11-316646
Chang HH, Lu MY, Liao YM, et al. Improved efficacy and tolerability of oral deferasirox by twice-daily dosing for patients with transfusion-dependent beta-thalassemia. Pediatr Blood Cancer. 2011;56:420-4. doi:10.1002/pbc.22826
Pennell DJ, Porter JB, Cappellini MD, et al. Deferasirox for up to 3 years leads to continued improvement of myocardial T2* in patients with β-thalassemia major. Haematologica. 2012;97:842-8. doi:10.3324/haematol.2011.049957
Pongtanakul B, Viprakasit V. Twice daily deferasirox significantly improves clinical efficacy in transfusion dependent thalassaemias who were inadequate responders to standard once daily dose. Blood Cells Mol Dis. 2013;51:96-7. doi:10.1016/j.bcmd.2013.03.004
Saiviroonporn P, Viprakasit V, Maneesai A, et al. Inter-site validations of the Pixel-Wise method for cardiac T2* analysis in transfusion-dependent Thai thalassemia patients. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. 2012;95 Suppl 2:S165-72
Chirnomas D, Smith AL, Braunstein J, et al. Deferasirox pharmacokinetics in patients with adequate versus inadequate response. Blood. 2009;114:4009-13. doi:10.1182/blood-2009-05-222729
Viprakasit V, Nuchprayoon I, Chuansumrit A, et al. Deferiprone (GPO-L-ONE(®) ) monotherapy reduces iron overload in transfusion-dependent thalassemias: 1-year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO-L-ONE; A001) from Thailand. Am J Hematol. 2013;88:251-60. doi:10.1002/ajh.23386
Takpradit C, Viprakasit V. Using of deferasirox and deferoxamine in refractory iron overload thalassemia. 2021;63:404-9. doi:10.1111/ped.14444
Otto-Duessel M, Aguilar M, Nick H, Moats R, Wood JC. Comparison of twice-daily vs once-daily deferasirox dosing in a gerbil model of iron cardiomyopathy. Experimental hematology. 2007;35:1069-73. doi:10.1016/j.exphem.2007.04.001
Salehifar E, Karami H, Kosaryan M, et al. Efficacy of Oral Deferasirox by Twice-daily Dosing in Patients with Transfusion-dependent Beta Thalassemia. Journal of Mazandaran University of Medical Sciences. 2015;25:1-8
Gumruk F, Unal S, Bayhan T, Hazirolan T, Tuncer AM, Cetin M. Twice Daily Use of Deferasirox Is More Effective in Decreasing Serum Ferritin. Blood. 2014;124:2675-. doi:10.1182/blood.V124.21.2675.2675
Karimi M, Haghpanah S, Bahoush G, et al. Evaluation of Efficacy, Safety, and Satisfaction Taking Deferasirox Twice Daily Versus Once Daily in Patients With Transfusion-Dependent Thalassemia. J Pediatr Hematol Oncol. 2020;42:23-6. doi:10.1097/mph.0000000000001596

How to Cite



“LONG-TERM EFFECTIVENESS, SAFETY, AND TOLERABILITY OF TWICE-DAILY DOSING WITH DEFERASIROX IN CHILDREN WITH TRANSFUSION-DEPENDENT THALASSEMIAS UNRESPONSIVE TO STANDARD ONCE-DAILY DOSING” (2021) Mediterranean Journal of Hematology and Infectious Diseases, 13(1), p. e2021065. doi:10.4084/MJHID.2021.065.
Copyright (c) 2021 Jassada Buaboonnam, Chayamon Takpradit, Vip Viprakasit, Nattee Narkbunnam, Nassawee Vathana, Kamon Phuakpet, Kleebsabai Sanpakit, Bunchoo Pongtanakul Creative Commons License

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