title: Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation.
abstract: Elevated serum ferritin contributes to treatment-related morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The multicenter DE02 trial assessed the safety, efficacy and impact of deferasirox on iron homeostasis after allogeneic HSCT. Deferasirox was administered at a starting dose of 10 mg/kg per day to 76 recipients of allogeneic HSCT, with subsequent dose adjustments based on efficacy and safety. Deferasirox was initiated at a median of 168 days after HSCT, with 84% of patients still on immunosuppression. Baseline serum ferritin declined from 2045 to 957 ng/mL. Deferasirox induced a negative iron balance in 84% of patients. Hemoglobin increased in the first 3 months, and trough serum cyclosporine levels were stable. Median exposure was 330 days, with a median compliance rate of >80%. The most common investigator-reported drug-related adverse events (AEs) were increased blood creatinine (26.5%), nausea (9.0%) and abdominal discomfort (8.3%). Fifty-four (71.1%) patients experienced drug-related AEs, which occasionally resulted in discontinuation (gastrointestinal (n=6), skin (n=3), elevated transaminases (n=1) and creatinine (n=1)). The incidence of AEs appeared to be dose related, with 7.5 mg/kg per day being the best-tolerated dose. Low-dose deferasirox is an effective chelation therapy after allogeneic HSCT, with a manageable safety profile, even in patients receiving cyclosporine.
authors.affiliation: Department of Hematology/Oncology, University Hospital of Leipzig, Leipzig, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Jaekel
authors.affiliation: Novartis Pharma GmbH, Nürnberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Lieder
authors.affiliation: Novartis Pharma GmbH, Nürnberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Albrecht
authors.affiliation: Novartis Pharma GmbH, Nürnberg, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Leismann
authors.affiliation: Department of Hematology/Oncology, University Hospital of Leipzig, Leipzig, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Hubert
authors.affiliation: Medizinische Klinik II, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Bug
authors.affiliation: University Hospital Hamburg, Hamburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Kröger
authors.affiliation: University of Dresden, Dresden, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Platzbecker
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stadler
authors.affiliation: University of Kiel, Kiel, Germany.
authors.forename: K
authors.initials: K
authors.lastname: de Haas
authors.affiliation: Molecular Medicine Partnership Unit and Department of Pediatric Oncology, Hematology and Immunology, University Clinic of Heidelberg, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Altamura
authors.affiliation: Molecular Medicine Partnership Unit and Department of Pediatric Oncology, Hematology and Immunology, University Clinic of Heidelberg, Heidelberg, Germany.
authors.forename: M U
authors.initials: MU
authors.lastname: Muckenthaler
authors.affiliation: Department of Hematology/Oncology, University Hospital of Leipzig, Leipzig, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Niederwieser
authors.affiliation: Department of Hematology/Oncology, University Hospital of Leipzig, Leipzig, Germany.
authors.forename: H K
authors.initials: HK
authors.lastname: Al-Ali
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D001565:Benzoates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D000077588:Deferasirox; D005260:Female; D005293:Ferritins / Q000097:blood*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007501:Iron / Q000097:blood*; D019189:Iron Metabolism Disorders / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D001565:Benzoates; D014230:Triazoles; D016572:Cyclosporine; D005293:Ferritins; D007501:Iron; D000077588:Deferasirox