Real life data: follow-up assessment on Spanish Gaucher disease patients treated with eliglustat. TRAZELGA project.

BACKGROUND: The availability of multiple treatments for type 1 Gaucher disease increases the need for real-life studies to evaluate treatment efficacy and safety and provide clinicians with more information to choose the best personalized therapy for their patients. AIMS: To determine whether treatment with eliglustat produces, in adult GD1 patients, ans optimal response in daily clinical practice. METHODS: We designed a real-life study with 2 years of follow-up (TRAZELGA [GEE-ELI-2017-01]) to uniformly evaluate the response and adverse events to eliglustat treatment. This study, conducted in 30 patients across Spain and previously treated with other therapies, included the evaluation of safety and efficacy by assessing visceral enlargement, bone disease (DEXA and T and Z scores), concomitant treatments and adverse events, as well as a quality of life evaluation (SF-36). In addition, the quantification of classical biomarkers (chitotriosidase activity, CCL18/PARC and glucosylsphingosine (GluSph)) and new candidates for GD biomarkers (YKL-40, cathepsin S, hepcidin and lipocalin-2 determined by immunoassay) were also assessed. Non-parametric statistical analysis was performed and p < 0.05 was considered statistically significant. MAIN RESULTS: Thirty patients were enrolled in the study. The median age was 41.5 years and the male-female ratio was 1.1:1. 84% of the patients had received ERT and 16% SRT as previous treatment. The most common symptoms at baseline were fatigue (42%) and bone pain (38%), no patient had a bone crisis during the study, and two years after switching, 37% had reduced their use of analgesics. Patient-reported outcomes showed a significant increase in physical function scores (p = 0.027) and physical pain scores (p = 0.010). None of the enrolled patients discontinued treatment due to adverse events, which were mild and transient in nature, mainly gastrointestinal and skin dryness. None of the biomarkers show a significant increase or decompensation after switching. CCL18/PARC (p = 0.0012), YKL-40 (p = 0.00004) and lipocalin-2 (p = 0.0155) improved after two years and GluSph after one year (p = 0.0008) and two years (p = 0.0245) of oral therapy. CONCLUSION: In summary, this real-life study, showed that eliglustat maintains stability and can improve quality of life with few side effects. Significant reductions in classic and other novel biomarkers were observed after two years of therapy.

Pure red cell aplasia in a simultaneous pancreas-kidney transplantation patient: inside the erythroblast.

A case of pure red cell aplasia in a simultaneous kidney-pancreas transplant recipient on immunosuppressive therapy is reported here. The patient presented with anemia unresponsive to erythropoietin treatment. Bone marrow cytomorphology was highly suggestive of parvovirus pure red cell aplasia, which was confirmed with serology and polymerase chain reaction positive for parvovirus B19 DNA in peripheral blood. After the administration of intravenous immunoglobulin the anemia improved with a rising number of the reticulocytes.

Long-term effect of liver transplantation on cirrhotic autonomic cardiac dysfunction.

There is little information on the long-term effect of liver transplantation (LT) on cardiac autonomic dysfunction in cirrhotic patients. We compared cardiac autonomic function before and in the long-term after LT. In a transversal study, we investigated 30 cirrhotics awaiting LT, 15 clinically stable patients 2-6 years after LT and 27 healthy controls. Seven cirrhotic patients were studied before LT, and 6, 12 and 33 months after LT, in a prospective fashion. Cardiac autonomic function was measured by heart rate variability (HRV) analysis during 24-h electrocardiogram recording. In the transversal study, patients with cirrhosis as compared to healthy controls had significantly reduced standard deviation of normal-to-normal RR intervals (SDNN) (p<0.001) and of the square root of the mean of squared differences between adjacent NN intervals (RMS-SD) (p<0.01), while the ratio between low frequency (LF) and high frequency (HF) at night was significantly (p<0.05) increased. Liver transplanted patients had significantly (p<0.001) higher SDNN values than cirrhotics, while RMS-SD and LF/HF at night did not differ. In the prospective study, SDNN progressively increased after LT and was significantly (p<0.05) higher at 12 and 33 months, compared to the pre-operative value. RMS-SD and LF/HF at night did not change after LT. In conclusion, the overall HRV decrease present in cirrhosis, measured by SDNN values, is partially corrected in the long-term after LT. However, parasympathetic impairment, measured by RMS-SD and LF/HF at night, is not affected even in the long-term after operation.