No abstract

Extracorporeal photochemotherapy (ECP) has been progressively introduced into the treatment of both acute and chronic graft-versus-host disease (cGvHD) over the last decade. Nevertheless, its mechanisms of action, as well as the optimal treatment schedule, have not yet been defined. We retrospectively analyzed 25 patients with cGvHD unresponsive to conventional treatments who underwent ECP from 1997 until 2005. The impact of various factors (such as treated and infused nucleated cells, time from transplantation and cGvHD onset, and time from cGvHD and ECP treatment) on the probability of no response to ECP was therefore investigated. A positive response to ECP was achieved in 80% of the patients, after a median of 19 ECP treatments (with a range of 8-38). Eighteen out of the 20 patients responsive to the treatment maintained their response for a median of 30 months. We mainly focused on clinical response and yield composition. The analysis on mononuclear cell (MNC) dose suggested that an increase of MNC dose/kg b.w. (body weight) induced a decrease in the odds of treatment failure, and that, if the MNC dose infused was at least 100 x 10(6)/kg b.w. per ECP treatment, a more positive and longer-lasting response was achieved. Moreover, the mean dose of treated and infused monocytes x 10(6)/kg b.w./ECP did not account for a clear dose-related effect. These findings may eventually result in a more patient-tailored approach to ECP. Prospective multicenter trials should be designed to investigate the real impact of MNC dose on ECP responsiveness.

A constant improvement in the performance of blood cell separators has been observed in recent years, allowing better yields in peripheral blood stem cell collection (PBSC) either from healthy donors or for autologous purposes. Nevertheless, to our knowledge, no reports on the efficiency of mononuclear cell (MNC) collection in patients undergoing extra-corporeal photochemotherapy (ECP) for graft-vs.-host-disease (GvHD) have been published. We retrospectively investigated the efficiency of 167 MNC collections performed consecutively in 12 patients between January 1999 and June 2001 by means of the COBE Spectra version 4.7 (V 4.7) or version 6.0 (V 6.0), for 109 and 58 procedures, respectively. MNC fractional extraction (FE) was higher in the V 6.0 group compared to the V 4.7 group : 0.59 +/- 0.21 vs. 0.51 +/- 0.22 (P < 0.05). However, platelet contamination was lower in the products obtained with V.6.0 compared to those obtained with V.4.7: 740 ( 630 x 10(3)/(L vs. 2,073 ( 1,429 x 10(3)/(L (P < 0.05). Only two patients with acute GvHD, both from V 4.7 group, required post-ECP platelet transfusion. The recently released version 6.0 allowed a satisfactory MNC yield with minimal platelet contamination in patients scheduled to undergo ECP for acute or chronic GvHD.

BACKGROUND:  The wide diffusion of multicomponent collection in donor apheresis has led to the yielding of different components, such as plasma‐reduced platelet‐pheresis at high PLT concentration. We investigated whether this collection modality could induce more PLT activation compared to standard plateletpheresis. STUDY DESIGN AND METHODS:  Forty‐one plateletpheresis collections (20 Trima and 21 Spectra LRS Turbo v.7.0, COBE) were evaluated. Donor, procedure, and product data were recorded. ADP, collagen, and U46619 (a thromboxane‐A2 analog)‐induced PLT aggregation was investigated in basal (donor) and final (plateletpheresis unit) samples. The expression of PLT activation marker P‐selectin (CD62P) was studied using flow cytometry in basal and final samples. In all cases, P‐selectin was investigated in final samples after stimulation with ADP to assess for a possible further release of the antigen. Four additional plateletpheresis procedures were performed in donors from Group A, using the traditional, nonplasma‐reduced program. RESULTS:  Plateletpheresis obtained by means of the Trima device showed a lower response to in‐vitro induced PLT aggregation and a higher percentage of P‐selectin‐expressing PLT when compared to products obtained using the Spectra device. Moreover, P‐selectin release after ADP stimulation was reduced in plateletpheresis units obtained using the Trima device. These differences disappeared when a nonplasma‐reduced collection program was used. In‐vivo evaluation did not detect any difference between platelepheresis obtained by means of the two cell separators. CONCLUSIONS:  Plateletpheresis units obtained by means of multicomponent collection show a higher degree of PLT activation compared to traditional plateletpheresis procedures when high‐concentration plasma‐reduced products are collected. Randomized clinical studies are needed to assess the real impact of these findings in terms of in‐vivo efficacy of plasma‐reduced plateletpheresis units.