PMID- 29155313
OWN - NLM
STAT- MEDLINE
DCOM- 20190305
LR  - 20190305
IS  - 1523-6536 (Electronic)
IS  - 1083-8791 (Linking)
VI  - 24
IP  - 3
DP  - 2018 Mar
TI  - A Phase II, Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of 
      Deferasirox after Hematopoietic Stem Cell Transplantation in Children with 
      beta-Thalassemia Major.
PG  - 613-618
LID - S1083-8791(17)30820-0 [pii]
LID - 10.1016/j.bbmt.2017.11.006 [doi]
AB  - 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 
      beta-thalassemia major (TM) who underwent hematopoietic stem cell transplantation 
      (HSCT) and had evidence of iron overload (serum ferritin >1000 microg/L; cardiac MRI 
      T2* <20 ms, or liver iron concentration [LIC; by MRI R2]  >/=5 mg/g). Patients 
      received deferasirox at an initial dose of 10 mg/kg/day, with up-titration to a 
      maximum of 20 mg/kg/day. The study continued for 52 weeks and included a total of 
      27 patients (mean age, 9.1 +/- 3.8 years; 70.4% male). One patient (3.7%) was lost 
      to follow-up. The majority of patients (n = 20; 74.1%) were able to achieve the 
      intended dose of 20 mg/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, n = 4; urinary tract infection, n = 1). 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 17.0 IU/L, and aspartate aminotransferase (AST), from 35.5 to 
      26.0 IU/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 1718.0 microg/L at baseline to 845.3 microg/L following 52 
      weeks of therapy (P < .001); 9 patients (33.3%) achieved a level of <500 microg/L. 
      There was also a significant decrease in median LIC (from 8.6 to 4.1 mg/g; 
      P < .001) and an increase in median cardiac T2* (from 26.0 to 28.0 ms; P = .520) 
      from baseline to week 52. Our findings indicate that deferasirox treatment at 
      doses up to 20 mg/kg/day reduces the iron burden in children with TM post-HSCT, 
      with a manageable safety profile.
CI  - Copyright (c) 2017 The American Society for Blood and Marrow Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Yesilipek, Mehmet Akif
AU  - Yesilipek MA
AD  - Pediatric Hematology, Medical Park Antalya Hospital, Antalya, Turkey. Electronic 
      address: yesilipek@gmail.com.
FAU - Karasu, Gulsun
AU  - Karasu G
AD  - Pediatric Hematology, Medical Park Goztepe Hospital, Istanbul, Turkey.
FAU - Kaya, Zuhre
AU  - Kaya Z
AD  - Pediatric Hematology, Faculty of Medicine, Gazi University, Ankara, Turkey.
FAU - Kuskonmaz, Baris B
AU  - Kuskonmaz BB
AD  - Pediatric Hematology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
FAU - Uygun, Vedat
AU  - Uygun V
AD  - Pediatric Hematology, Medical Park Antalya Hospital, Antalya, Turkey.
FAU - Dag, Ilkiz
AU  - Dag I
AD  - Novartis Oncology, Istanbul, Turkey.
FAU - Ozudogru, Onur
AU  - Ozudogru O
AD  - Novartis Oncology, Istanbul, Turkey.
FAU - Ertem, Mehmet
AU  - Ertem M
AD  - Pediatric Hematology, Faculty of Medicine, Ankara University, Ankara, Turkey.
LA  - eng
SI  - ClinicalTrials.gov/NCT01610297
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20171116
PL  - United States
TA  - Biol Blood Marrow Transplant
JT  - Biology of blood and marrow transplantation : journal of the American Society for 
      Blood and Marrow Transplantation
JID - 9600628
RN  - 9007-73-2 (Ferritins)
RN  - V8G4MOF2V9 (Deferasirox)
SB  - IM
MH  - Adolescent
MH  - Allografts
MH  - Child
MH  - Child, Preschool
MH  - Deferasirox/*administration & dosage/adverse effects
MH  - Female
MH  - Ferritins/*blood
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - *Iron Overload/blood/etiology/prevention & control
MH  - Male
MH  - *beta-Thalassemia/blood/therapy
OTO - NOTNLM
OT  - Bone marrow transplant
OT  - Iron chelation
OT  - Iron overload
OT  - Transfusion-dependent thalassemia
EDAT- 2017/11/21 06:00
MHDA- 2019/03/06 06:00
CRDT- 2017/11/21 06:00
PHST- 2017/03/13 00:00 [received]
PHST- 2017/11/02 00:00 [accepted]
PHST- 2017/11/21 06:00 [pubmed]
PHST- 2019/03/06 06:00 [medline]
PHST- 2017/11/21 06:00 [entrez]
AID - S1083-8791(17)30820-0 [pii]
AID - 10.1016/j.bbmt.2017.11.006 [doi]
PST - ppublish
SO  - Biol Blood Marrow Transplant. 2018 Mar;24(3):613-618. doi: 
      10.1016/j.bbmt.2017.11.006. Epub 2017 Nov 16.