Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8430160 | Biology of Blood and Marrow Transplantation | 2018 | 27 Pages |
Abstract
We conducted a prospective, phase II, multicenter, single-arm study to evaluate the efficacy and safety of deferasirox in patients age >2 to <18 years with β-thalassemia major (TM) who underwent hematopoietic stem cell transplantation (HSCT) and had evidence of iron overload (serum ferritin >1000âµg/L; cardiac MRI T2*â<20âms, or liver iron concentration [LIC; by MRI R2]â â¥5âmg/g). Patients received deferasirox at an initial dose of 10âmg/kg/day, with up-titration to a maximum of 20âmg/kg/day. The study continued for 52 weeks and included a total of 27 patients (mean age, 9.1â±â3.8 years; 70.4% male). One patient (3.7%) was lost to follow-up. The majority of patients (nâ=â20; 74.1%) were able to achieve the intended dose of 20âmg/kg/day. No deaths occurred. A total of 134 adverse events (AEs) were reported in 25 patients (92.6%) during the study. The majority of patients had grade 1 or 2 AEs, with only 8 patients (29.6%) experiencing grade 3 AEs. Only 10 AEs occurring in 4 patients (14.8%) were suspected to be related to deferasirox (ALT/AST increase, nâ=â4; urinary tract infection, nâ=â1). The deferasirox dose had to be adjusted or interrupted for 6 AEs occurring in 4 patients (14.8%). A total of 6 serious AEs occurred in 3 patients (11.1%), none of which were suspected to be related to deferasirox. From baseline to week 52, there were decreases in median concentrations of alanine aminotransferase (ALT), from 30.0 to 17.0âIU/L, and aspartate aminotransferase (AST), from 35.5 to 26.0âIU/L. Median serum creatinine and cystatin C concentrations were similar at baseline and week 52. There was a continuous and significant decrease in median serum ferritin level from 1718.0âµg/L at baseline to 845.3âµg/L following 52 weeks of therapy (Pâ<â.001); 9 patients (33.3%) achieved a level of <500âµg/L. There was also a significant decrease in median LIC (from 8.6 to 4.1âmg/g; Pâ<â.001) and an increase in median cardiac T2* (from 26.0 to 28.0âms; Pâ=â.520) from baseline to week 52. Our findings indicate that deferasirox treatment at doses up to 20âmg/kg/day reduces the iron burden in children with TM post-HSCT, with a manageable safety profile.
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Authors
Mehmet Akif Yesilipek, Gulsun Karasu, Zuhre Kaya, Baris B. Kuskonmaz, Vedat Uygun, Ilkiz Dag, Onur Ozudogru, Mehmet Ertem,