Background and Objectives A photochemical treatment process (PCT) utilizing amotosalen and UVA light (INTERCEPT™ Blood System) has been developed for inactivation of viruses, bacteria, parasites and leucocytes that can contaminate blood components intended for transfusion. The objective of this study was to further characterize the safety profile of INTERCEPT‐treated platelet components (PCT‐PLT) administered across a broad patient population. Materials and Methods This open‐label, observational haemovigilance programme of PCT‐PLT transfusions was conducted in 21 centres in 11 countries. All transfusions were monitored for adverse events within 24 h post‐transfusion and for serious adverse events (SAEs) up to 7 days post‐transfusion. All adverse events were assessed for severity (Grade 0–4), and causal relationship to PCT‐PLT transfusion. Results Over the course of 7 years in the study centres, 4067 patients received 19 175 PCT‐PLT transfusions. Adverse events were infrequent, and most were of Grade 1 severity. On a per‐transfusion basis, 123 (0·6%) were classified an acute transfusion reaction (ATR) defined as an adverse event related to the transfusion. Among these ATRs, the most common were chills (77, 0·4%) and urticaria (41, 0·2%). Fourteen SAEs were reported, of which 2 were attributed to platelet transfusion (<0·1%). No case of transfusion‐related acute lung injury, transfusion‐associated graft‐versus‐host disease, transfusion‐transmitted infection or death was attributed to the transfusion of PCT‐PLT. Conclusion This longitudinal haemovigilance safety programme to monitor PCT‐PLT transfusions demonstrated a low rate of ATRs, and a safety profile consistent with that previously reported for conventional platelet components.

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We evaluated the association of diabetes and insulin resistance with the response to cell therapy in patients with nonischemic dilated cardiomyopathy (DCM). A total of 45 outpatients with DCM received granulocyte colony-stimulating factor for 5 days. CD34 + cells were then collected by apheresis and injected transendocardially. Twelve patients had diabetes mellitus (DM group), 17 had insulin resistance (IR group), and 16 displayed normal glucose metabolism (no-IR group). After stimulation, we found higher numbers of CD34 + cells in the IR group (94 6 73 3 10 6 cells per liter) than in the no-IR group (54 6 35 3 10 6 cells per liter) or DM group (31 6 20 3 10 6 cells per liter; p = .005). Similarly, apheresis yielded the highest numbers of CD34 + cells in the IR group (IR group, 216 6 110 3 10 6 cells; no-IR group, 127 6 82 3 10 6 cells; DM group, 77 6 83 3 10 6 cells; p = .002). Six months after cell therapy, we found an increase in left ventricular ejection fraction in the IR group (+5.6% 6 6.9%) and the no-IR group (+4.4% 6 7.2%) but not in the DM group (20.9% 6 5.4%; p = .035). The N-terminal probrain natriuretic peptide levels decreased in the IR and no-IR groups, but not in the DM group (2606 6 850 pg/ml; 2698 6 1,105 pg/ml; and +238 6 963 pg/ml, respectively; p = .034). Transendocardial CD34+ cell therapy appears to be ineffective in DCM patients with diabetes. IR was associated with improved CD34 + stem cell mobilization and a preserved clinical response to cell therapy. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:632-638 SIGNIFICANCEThe present study is the first clinical study directly evaluating the effects of altered glucose metabolism on the efficacy of CD34 + stem cell therapy in patients with nonischemic dilated cardiomyopathy. The results offer critical insights into the physiology of stem cell mobilization in heart failure and possibly an explanation for the often conflicting results obtained with stem cell therapy for heart failure. These results demonstrate that patients with dilated cardiomyopathy and diabetes do not benefit from autologous CD34 + cell therapy. This finding could serve as a useful tool when selecting heart failure patients for future clinical studies in the field of stem cell therapy.

Background-We investigated the effects of transendocardial CD34+ cell transplantation in patients with ischemic cardiomyopathy. Methods and Results-In a prospective crossover study, we enrolled 33 patients with ischemic cardiomyopathy with New York Heart Association class III and left ventricular ejection fraction <40%. In phase 1, patients were treated with medical therapy for 6 months. Thereafter, all patients underwent transendocardial CD34 + cell transplantation. Peripheral blood CD34 + cells were mobilized by granulocyte colony stimulating factor, collected via apheresis, and injected transendocardially in the areas of hibernating myocardium. Patients were followed up for 6 months after the procedure (phase 2). Two patients died during phase 1 and none during phase 2. The remaining 31 patients were 85% men, aged 57±6 years. In phase 1, we found no change in left ventricular ejection fraction (from 25.2±6.2% to 27.1±6.6%; P=0.23), N-terminal pro B-type natriuretic peptide (from 3322±3411 to 3672±5165 pg/mL; P=0.75) or 6-minute walk distance (from 373±68 to 411±116 m; P=0.17). In contrast, in phase 2 there was an improvement in left ventricular ejection fraction (from 27.1±6.6% to 34.9±10.9%; P=0.001), increase in 6-minute walk distance (from 411±116 to 496±113 m; P=0.001), and a decrease in N-terminal pro B-type natriuretic peptide (from 3672±5165 to 1488±1847 pg/mL; P=0.04). The average number of injected CD34 + cells was 90.6±7.5×106 . Higher doses of CD34 + cells and a more diffuse distribution of transendocardial cell injections were associated with better clinical response. Conclusions-Transendocardial CD34+ cell transplantation may be associated with improved left ventricular function, decreased N-terminal pro B-type natriuretic peptide levels, and better exercise capacity in patients with ischemic cardiomyopathy. These effects seem to be particularly pronounced in patients receiving diffusely distributed cell injections and high-dose cell therapy. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01350310.(Circ Cardiovasc Interv. 2014;7:552-559.)