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GvHD, the most important cause of morbidity and mortality after allogeneic stem cell transplantation, depends primarily on the ability of a donor T-cell subset to react to immunogenic host Ag. Recently developed culture conditions and treatment strategies may bring us closer to the selective elimination of such alloreactive T cells, often considered the holy grail of transplantation. Among the various therapeutic modalities, photodynamic therapy (PDT) offers a biological and global approach to the eradication of unwanted allo-activated T cells by combining mitochondrial targeting, P-glycoprotein inhibition and reactive oxygen species production. Indeed, the high potency of PDT against malignant cells has been harnessed to exert selective and extensive elimination of alloreactive T-cell subsets mediating GvHD, while preserving resting T cells with the ability to reconstitute the immune system for GvL activity and prevent or suppress viruses and fungi. The present paper reviews the basis of the PDT strategy, and the methodology employed. In vitro and in vivo studies that formed the proof of principle as a basis for human studies to investigate the clinical potential of PDT in the context of GvHD will be presented together with insights into future clinical applications of this versatile treatment platform. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many hematologic malignancies and inherited disorders of the hematopoietic system. Ex vivo T-cell depletion (TCD) of the graft and post-transplantation immunosuppression efficiently prevents the development of GvHD in no- MHC-identical settings. However, the consequence of these non-specific strategies is a long-lasting immunodeficiency associated with increased incidence of disease relapse, graft rejection and reactivation of viral infections. Donor lymphocyte infusion, which is used for treating leukemic relapse after allogeneic HSCT, can result in severe GvHD. Several strategies are being optimized specifically to inactivate anti-host T cells while preserving anti-leukemic or anti-microbial immunocompetence. Based on the ex vivo or in vivo elimination of anti-host T cells, or on the modulation of their anti-host activity, these approaches, which have been explored extensively in pre-clinical studies and tested in some preliminary clinical trials, are discussed in this paper. [ABSTRACT FROM AUTHOR]

Background aims. Immunomagnetic cell selection (ICS) of CD34+ cells is being used increasingly in allogeneic transplantation in order to reduce T-cell quantity. The aim of this study was to evaluate an automated washing protocol before immunomagnetic selection. Methods. The automated method was compared with a conventional washing procedure. In the study group the cell processing using the automated procedure, both before and after antibody incubation, was performed with a Sepax S-100 device. The efficacy of the automated procedure was compared with the control group, where washing were performed using a standard method. Results. The results obtained after pre-incubation washing performed using the automated system showed a total nucleated cell (NC) and CD34+ cell recovery of 84.87% (71.80-105, SD 8.62; range, standard deviation) and 83.45% (47-109, SD 16.12), respectively. The NC and CD34+ cell recovery after the pre-incubation washing cycle was performed using the standard method was 75.54% (38.36-97.76, SD 22.5) and 61.51% (30.87-81.79, SD 19.3), respectively. The CD34+ cell recovery after ICS was 51.27% (13.77-98.82, SD 24.97) and 48.89% (15.57-88.24, SD 25.91) for group 1 and group 2, respectively. The average purity in group 1 was 86.46% (67.4-96.10, SD 13.07) and in group 2 84.97% (58.1-97.8, SD 15.58). Conclusions. The efficacy of the ICS led to an optimal purity without affecting cell recovery, which was higher in group 1. Overall, our data suggest that the automated method is suitable for washing hematopoietic progenitor cell apheresis (HPC-A) concentrates before immunomagnetic cell selection in daily clinical routines. [ABSTRACT FROM AUTHOR]