Open AccessLONG-TERM EFFECTIVENESS, SAFETY, AND TOLERABILITY OF TWICE-DAILY DOSING WITH DEFERASIROX IN CHILDREN WITH TRANSFUSION-DEPENDENT THALASSEMIAS UNRESPONSIVE TO STANDARD ONCE-DAILY DOSING
Author(s) -
Jassada Buaboonnam,
Chayamon Takpradit,
Vip Viprakasit,
Nattee Narkbunnam,
Nassawee Vathana,
Kamon Phuakpet,
Kleebsabai Sanpakit,
Bunchoo Pongtanakul
Publication year - 2021
Publication title -
mediterranean journal of hematology and infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.682
H-Index - 31
ISSN - 2035-3006
DOI - 10.4084/mjhid.2021.065
Subject(s) - deferasirox , medicine , tolerability , dosing , adverse effect , refractory (planetary science) , gastroenterology , deferoxamine , blood transfusion , thalassemia , physics , astrobiology
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.