LONG-TERM EFFECTIVENESS, SAFETY, AND TOLERABILITY OF TWICE-DAILY DOSING WITH DEFERASIROX IN CHILDREN WITH TRANSFUSION-DEPENDENT THALASSEMIAS UNRESPONSIVE TO STANDARD ONCE-DAILY DOSING
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-concen...
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PAGEPress Publications
2021-10-01
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| Series: | Mediterranean Journal of Hematology and Infectious Diseases |
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| Online Access: | http://mjhid.org/index.php/mjhid/article/view/4720 |
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| author | Jassada Buaboonnam Chayamon Takpradit Vip Viprakasit Nattee Narkbunnam Nassawee Vathana Kamon Phuakpet Kleebsabai Sanpakit Bunchoo Pongtanakul |
| author_facet | Jassada Buaboonnam Chayamon Takpradit Vip Viprakasit Nattee Narkbunnam Nassawee Vathana Kamon Phuakpet Kleebsabai Sanpakit Bunchoo Pongtanakul |
| author_sort | Jassada Buaboonnam |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b82ef7811f6941f09de4fb43a3f6941d |
| institution | Kabale University |
| issn | 2035-3006 |
| language | English |
| publishDate | 2021-10-01 |
| publisher | PAGEPress Publications |
| record_format | Article |
| series | Mediterranean Journal of Hematology and Infectious Diseases |
| spelling | doaj-art-b82ef7811f6941f09de4fb43a3f6941d2024-12-02T02:06:08ZengPAGEPress PublicationsMediterranean Journal of Hematology and Infectious Diseases2035-30062021-10-0113110.4084/MJHID.2021.065LONG-TERM EFFECTIVENESS, SAFETY, AND TOLERABILITY OF TWICE-DAILY DOSING WITH DEFERASIROX IN CHILDREN WITH TRANSFUSION-DEPENDENT THALASSEMIAS UNRESPONSIVE TO STANDARD ONCE-DAILY DOSINGJassada Buaboonnam0Chayamon Takpradit1Vip Viprakasit2Nattee Narkbunnam3Nassawee Vathana4Kamon Phuakpet5Kleebsabai Sanpakit6Bunchoo Pongtanakul7a:1:{s:5:"en_US";s:35:"Siriraj Hospital Mahidol University";}Division of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDivision of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDivision of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDivision of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDivision of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDivision of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDivision of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandBackground: 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.http://mjhid.org/index.php/mjhid/article/view/4720deferasiroxIron chelationIron OverloadThalassemia |
| spellingShingle | Jassada Buaboonnam Chayamon Takpradit Vip Viprakasit Nattee Narkbunnam Nassawee Vathana Kamon Phuakpet Kleebsabai Sanpakit Bunchoo Pongtanakul LONG-TERM EFFECTIVENESS, SAFETY, AND TOLERABILITY OF TWICE-DAILY DOSING WITH DEFERASIROX IN CHILDREN WITH TRANSFUSION-DEPENDENT THALASSEMIAS UNRESPONSIVE TO STANDARD ONCE-DAILY DOSING Mediterranean Journal of Hematology and Infectious Diseases deferasirox Iron chelation Iron Overload Thalassemia |
| title | LONG-TERM EFFECTIVENESS, SAFETY, AND TOLERABILITY OF TWICE-DAILY DOSING WITH DEFERASIROX IN CHILDREN WITH TRANSFUSION-DEPENDENT THALASSEMIAS UNRESPONSIVE TO STANDARD ONCE-DAILY DOSING |
| title_full | LONG-TERM EFFECTIVENESS, SAFETY, AND TOLERABILITY OF TWICE-DAILY DOSING WITH DEFERASIROX IN CHILDREN WITH TRANSFUSION-DEPENDENT THALASSEMIAS UNRESPONSIVE TO STANDARD ONCE-DAILY DOSING |
| title_fullStr | LONG-TERM EFFECTIVENESS, SAFETY, AND TOLERABILITY OF TWICE-DAILY DOSING WITH DEFERASIROX IN CHILDREN WITH TRANSFUSION-DEPENDENT THALASSEMIAS UNRESPONSIVE TO STANDARD ONCE-DAILY DOSING |
| title_full_unstemmed | LONG-TERM EFFECTIVENESS, SAFETY, AND TOLERABILITY OF TWICE-DAILY DOSING WITH DEFERASIROX IN CHILDREN WITH TRANSFUSION-DEPENDENT THALASSEMIAS UNRESPONSIVE TO STANDARD ONCE-DAILY DOSING |
| title_short | LONG-TERM EFFECTIVENESS, SAFETY, AND TOLERABILITY OF TWICE-DAILY DOSING WITH DEFERASIROX IN CHILDREN WITH TRANSFUSION-DEPENDENT THALASSEMIAS UNRESPONSIVE TO STANDARD ONCE-DAILY DOSING |
| title_sort | long term effectiveness safety and tolerability of twice daily dosing with deferasirox in children with transfusion dependent thalassemias unresponsive to standard once daily dosing |
| topic | deferasirox Iron chelation Iron Overload Thalassemia |
| url | http://mjhid.org/index.php/mjhid/article/view/4720 |
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