Benserazide as a potential novel fetal hemoglobin inducer: an observational study in non-carriers of hemoglobin disorders.

Induction of fetal hemoglobin production with hydroxyurea is an effective strategy in sickle cell disease and beta thalassemias, but up to 20% of patients do not respond to or cannot tolerate it. Benserazide is used in the treatment of Parkinson's disease and was noticed to induce gamma globin in preclinical models. We hypothesized that chronic treatment with benserazide-containing medication may be associated with increase in HbF production and in circulating F-cells. Blood samples were collected from 50 subjects including 35 patients on benserazide for Parkinson's disease, 10 healthy controls, and 5 patients with sickle cell anemia as positive controls for high fetal hemoglobin. We found a strong correlation between HbF and circulating F-cells in the entire population, but we found no significant increase in HbF and F-cell percentage in patients taking benserazide up to 700 mg daily. No hematologic abnormalities attributable to benserazide use after up to 22 years were detected. Our data support long-term safety and tolerability of benserazide at doses ten times higher than used in preclinical models to induce fetal hemoglobin. Further clinical trials enrolling patients with sickle cell disease and thalassemia are warranted to provide insight into its efficacy to treat those populations.

Myocardial Iron Overload in Sickle Cell Disease: A Rare But Potentially Fatal Complication of Transfusion.

Sickle cell disease (SCD) is a frequent indication for chronic transfusion, which can cause iron overload. Excess iron often affects the liver, but not the heart in SCD. Magnetic resonance (MR) is recommended to detect myocardial iron overload (MIO) but its elevated cost requires optimized indication. We aimed to compile all published data on MIO in SCD upon the description of a fatal case of severe MIO in our institution, and to determine associated risk factors. We performed a systematic review using the PRISMA guidelines in two databases (PubMed and Web of Science). Inclusion criteria were publication in English, patients diagnosed with SCD, and reporting ferritin and MIO by MR. Twenty publications reported on 865 SCD adult and pediatric patients, with at least 10 other cases of MIO. The prevalence of MIO in chronically transfused SCD patients can be estimated to be 3% or less, and is associated with high transfusion burden, top-up transfusions, and low adherence to iron chelation. Cardiac siderosis in SCD is rarely reported, and increased awareness with better use of the available screening tools are necessary. Prospective studies should define the recommended chelation regimens depending on the severity of MIO.