Automated production of specific T cells for treatment of refractory viral infections after allogeneic stem cell transplantation.

Therapy-resistant viral reactivations contribute significantly to mortality after hematopoietic stem cell transplantation. Adoptive cellular therapy with virus-specific T cells (VST) has shown efficacy in various single-center trials. However, the scalability of this therapy is hampered by laborious production methods. In this study we describe the in-house production of VST in a closed system (CliniMACS Prodigy® system, Miltenyi Biotec). In addition, we report the efficacy in 26 patients with viral disease following hematopoietic stem cell transplantation in a retrospective analysis (adenovirus, n=7; cytomegalovirus, n=8; Epstein-Barr virus, n=4; multi-viral, n=7). The production of VST was successful in 100% of cases. The safety profile of VST therapy was favorable (n=2 grade 3 and n=1 grade 4 adverse events; all three were reversible). A response was seen in 20 of 26 patients (77%). Responding patients had a significantly better overall survival than patients who did not respond (P<0.001). Virus-specific symptoms were reduced or resolved in 47% of patients. The overall survival of the whole cohort was 28% after 6 months. This study shows the feasibility of automated VST production and safety of application. The scalability of the CliniMACS Prodigy® device increases the accessibility of VST treatment.

Three-dimensional assessment of extracranial Doppler sonography in carotid artery stenosis compared with digital subtraction angiography.

BACKGROUND AND PURPOSE: Difficulties in data presentation, data storage, and a high interobserver variability may influence color-coded Duplex sonography assessment of internal carotid artery stenosis (ICAS). The aim of our study was to evaluate the between-method agreement of ICAS using 3D color Doppler sonography (CDS) compared with digital subtraction angiography (DSA). METHODS: Forty-nine patients with 64 ICASs (age 64+/-9 years) were involved. The patients were investigated with a color-coded duplex system using the power mode. The 3D system consists of an electromagnet that induces a low-intensity magnetic field near the patient's head. A magnetic position sensor is attached to the probe and transmits the spatial orientation to a personal computer. RESULTS: A total of 62 ICASs were reconstructed successfully with 3D CDS in 47 of 49 patients. High agreement for 2 independent observers was found in 3D CDS (weighted kappa coefficient of 0.88). Three-dimensional CDS slightly underestimated the mean stenotic degree (mean 3D CDS 68.47+/-10.5 versus DSA 71.3+/-10.0). The intermethod agreement comparing DSA with 3D CDS was analyzed with the Bland and Altman test, which showed good agreement. Mean sensitivity of 3D CDS was 93%, mean specificity 82.5%, mean positive predictive value 82%, and mean negative predictive value 98%. CONCLUSIONS: The 3D CDS findings demonstrated good agreement compared with the gold standard, DSA, yielding higher accuracy than CDS alone. Compared with angiography or magnetic resonance angiography, 3D CDS can be performed easily on critically ill patients in stroke or intensive care units and may therefore provide a useful tool for patients unable to undergo more invasive imaging techniques.