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Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis that results in peripheral cytopenias. Anemia is the most common symptom of MDS and the majority of patients become transfusion-dependent with the risk of iron overload, which may lead to cardiac, hepatic and endocrine complications. Deferasirox is an orally available iron chelator administered once-daily in transfusion-dependent patients with various chronic anemias. Its efficacy has been established in controlled clinical trials. In the present study, we describe our experience with 55 consecutive MDS patients [International Prognostic Scoring System risk score of low (n=32) or intermediate-1 (n=23)] treated with deferasirox in a routine clinical setting following Consensus Guidelines on Iron Chelation Therapy. According to WHO classifications, patients had refractory anemia (n=30), refractory anemia with ringed sideroblasts (n=16), refractory cytopenia with multilineage dysplasia (n=8) or refractory cytopenia with multilineage dysplasia and ringed sideroblasts (n=1). The median monthly transfusion requirement at baseline was 3 units. Patients received a starting dosage of 10 mg/kg/day, subsequently titrated according to serum ferritin (SF) levels which were measured monthly. Safety assessment included monitoring of liver and renal parameters and recording adverse events (AE) during treatment. At the baseline, the mean ± SD SF level was 2,362±172 ng/ml and after 24 months, the mean ± SD decrease in SF was 1,679±209 ng/ml. Sixteen patients had sustained hematological improvement meeting International Working Group 2006 criteria. One patient became transfusion-independent. No severe AE were reported. In conclusion, deferasirox therapy was effective and safe in reducing transfusional iron overload and it reduces transfusion requirement in a subset of patients.

Principally located in the outer mitochondrial membrane, the translocator protein (TSPO) is an 18-kDa transmembrane protein that is a key component of the mitochondrial permeability transition pore. TSPO is associated with a number of biological processes, including apoptosis, the regulation of cellular proliferation, porphyrin transport and heme biosynthesis, immunomodulation, anion transport and the regulation of steroidogenesis. Thus, numerous studies have proposed TSPO as a promising target for novel therapeutic agents, particularly for the treatment of cancer. In the present study, the response of 30 consecutive chronic lymphocytic leukemia (CLL) patients to bendamustine and rituximab treatment was evaluated according to TSPO expression levels. Furthermore, thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO) levels, as well as caspase-3 activity were determined. Compared with the lymphocytes of healthy donors, the 30 consecutive CLL patients exhibited increased TSPO expression levels, decreased TBARS and NO levels and reduced caspase-3 activity. Six months after the treatment commenced, the TSPO/mitochondria ratio resembled that of the healthy controls in 24/30 CLL patients. In addition, an increase in TBARS and NO levels, two markers of oxidative stress, and a potentiation of caspase-3 activity in all responder patients was observed. Notably, the six patients who appeared to be resistant to treatment also displayed higher TSPO levels, and lower caspase-3 activity and TBARS levels. These data indicate that TSPO expression may be a molecular prognostic factor in CLL patients.