Τίτλος:
Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: Efficacy and safety during 5 years' follow-up
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Patients with β-thalassemia require lifelong iron chelation therapy from early childhood to prevent complications associated with transfusional iron overload. To evaluate long-term efficacy and safety of once-daily oral iron chelation with deferasirox, patients aged ≥ 2 years who completed a 1-year, phase 3, randomized trial entered a 4-year extension study, either continuing on deferasirox (deferasirox cohort) or switching from deferoxamine to deferasirox (crossover cohort). Of 555 patients who received ≥ 1 deferasirox dose, 66.8% completed the study; 43 patients (7.7%) discontinued because of adverse events. In patients with ≥ 4 years' deferasirox exposure who had liver biopsy, mean liver iron concentration significantly decreased by 7.8 ± 11.2 mg Fe/g dry weight (dw; n = 103; P < .001) and 3.1 ± 7.9 mg Fe/g dw (n = 68; P < .001) in the deferasirox and crossover cohorts, respectively. Median serum ferritin significantly decreased by 706 ng/mL (n = 196; P < .001) and 371 ng/mL (n = 147; P < .001), respectively, after ≥ 4 years'exposure. Investigator-assessed, drug-related adverse events, including increased blood creatinine (11.2%), abdominal pain (9.0%), and nausea (7.4%), were generally mild to moderate, transient, and reduced in frequency over time. No adverse effect was observed on pediatric growth or adolescent sexual development. This first prospective study of long-term deferasirox use in pediatric and adult patients with β- thalassemia suggests treatment for ≤ 5 years is generally well tolerated and effectively reduces iron burden. This trial was registered at www.clinicaltrials-.gov as #NCT00171210. © 2011 by The American Society of Hematology.
Συγγραφείς:
Cappellini, M.D.
Bejaoui, M.
Agaoglu, L.
Canatan, D.
Capra, M.
Cohen, A.
Drelichman, G.
Economou, M.
Fattoum, S.
Kattamis, A.
Kilinc, Y.
Perrotta, S.
Piga, A.
Porter, J.B.
Griffel, L.
Dong, V.
Clark, J.
Aydinok, Y.
Περιοδικό:
Blood advances
Εκδότης:
American Society of Hematology
Λέξεις-κλειδιά:
deferasirox; ferritin; iron, abdominal pain; adolescent; adult; article; cardiopulmonary arrest; child; child growth; cholelithiasis; congestive heart failure; controlled study; creatinine blood level; crossover procedure; diarrhea; dose response; drug efficacy; drug eruption; drug exposure; drug fever; drug safety; drug use; drug withdrawal; female; ferritin blood level; follow up; glucosuria; human; hypersplenism; hypertransaminasemia; iron chelation; iron overload; liver biopsy; liver level; major clinical study; male; myocardial dysfunction; nausea; preschool child; priority journal; school child; sexual development; side effect; thalassemia major; vomiting
DOI:
10.1182/blood-2010-11-316646
