title: Deferasirox in MDS patients with transfusion-caused iron overload--a phase-II study.
abstract: Blood transfusions represent a main component of supportive care in myelodysplastic syndromes (MDS). To avoid organ damage caused by transfusion-dependent iron overload, an adequate iron chelation therapy is required. Recently, a new oral iron chelator deferasirox (ICL670, Exjade) has become available. A study was conducted to demonstrate the efficacy and tolerability of deferasirox in transfusion-dependent iron-overloaded patients with MDS. The efficacy of deferasirox was monitored by changes in serum ferritin, bone marrow iron, and liver iron concentration (LIC), as determined by T2*-weighted magnetic resonance imaging. Twelve patients with MDS of different subtypes (median age 76 years, range 53-91) were enrolled. Deferasirox administered in a once-daily dose of 20-30 mg/kg for 12 months was effective in reducing median ferritin concentration from 1,515 microg/L (range 665-6,900) to 413 microg/L (range 105-3,052). Within the first 4 weeks of treatment before the continuous decline of ferritin levels, the values markedly rose in eight of 12 patients. The median LIC declined from 315 to 230 micromol/g (p=0.02) at the end of study, accompanied by a reduction of bone marrow siderosis. The most common adverse events were mild and transient gastrointestinal disturbances, skin rash, nonprogressive transient increases in serum creatinine and urine beta2-microglobulin, and a temporary reduction of the creatinine clearance. The renal parameters normalized after end of treatment. No hematologic toxicities were observed. Deferasirox proved to be effective in transfusion-dependent iron overload in MDS by mobilizing iron deposits in liver and at least stabilizing iron stores in bone marrow.
authors.affiliation: III. Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Wiesbadener Str. 7-11, 68305 Mannheim, Germany.
authors.forename: Georgia
authors.initials: G
authors.lastname: Metzgeroth
authors.forename: Dietmar
authors.initials: D
authors.lastname: Dinter
authors.forename: Beate
authors.initials: B
authors.lastname: Schultheis
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dorn-Beineke
authors.forename: Kira
authors.initials: K
authors.lastname: Lutz
authors.forename: Oliver
authors.initials: O
authors.lastname: Leismann
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hehlmann
authors.forename: Jan
authors.initials: J
authors.lastname: Hastka