The effect of pre-storage whole-blood leukocyte reduction on cytokines/chemokines levels in autologous CPDA-1 whole blood.

BACKGROUND: In this study, we aimed to investigate the effectiveness of pre-storage leukocyte filtration of autologous blood (AB), especially focusing on the cytokines/chemokines accumulation on blood products. MATERIALS AND METHODS: After approval of the ethics committee of the University of Tokyo, a total of 26 orthopedic patients, who donated AB prior to surgery after informed consent, were enrolled. The effects of filtration on blood cell counts were analyzed, and the accumulation of cytokines and chemokines were measured on pre- and post-leukoreduced (LR) samples, using the Luminex system. The time-dependent changes of the cytokines/chemokines and the effect of the filtration on their concentration were analyzed, and compared with the normal plasma levels reported in the literature. RESULTS: LR effectively reduced the number of leukocytes and platelets, without affecting that of red cells. The concentration of most of the cytokines/chemokines analyzed, except the EGF, sCD40-L and sFas-L, decreased time-dependently of storage or did not change in pre-LR samples. However, EGF, sCD40L and sFas-L were significantly reduced by LR. Some, such as IL-8 and RANTES, were also importantly decreased by LR, and others, such as IL-1ß and TNF-α, were not significantly affected by LR. CONCLUSIONS: Leukocyte filtration effectively removes platelets and leukocytes from AB, thus preventing the accumulation of cytokines/chemokines. Since adverse effects due to AB transfusion, although rare, are observed, there is need to consider the implementation of pre-storage leukocyte reduction (PSLR) for AB.

The current status of autologous blood transfusion in Japan--the importance of pre-deposit autologous blood donation program and the needs to achieve patient blood management.

BACKGROUND: Autologous blood transfusion (ABT) is currently considered the safest transfusion, since the risks of allogeneic immunological reaction and viral transmission are theoretically null. Although its use has declined in Western countries in the recent decade, it has been progressively expanded in Japan. With the widening of the concept of patient blood management (PBM), which aims to prevent the harmful adverse effects of the exposure to allogeneic blood, the importance of the ABT has once again gained interest. STUDY DESIGN AND METHODS: Here, we retrospectively analyzed the cases pre-depositing autologous blood for an elective surgery in the period of January 2000 to December 2010 in our hospital, where a pre-deposit autologous blood donation (PAD) program has been established in 2006, in an attempt to analyze the improvements achieved, and the problems remaining to achieve patient blood management. RESULTS: The PAD program contributed for the further improvement of ABT, and the number of participating patients increased, especially in the period 2002-2003, when the idea of PAD program implementation came out. By simple extrapolation of the ABT data to allogeneic blood, ABT was found to be superior in terms of cost-effectiveness. However, problems such as the high wastage rate, and the inappropriate transfusion triggers remain to be solved. CONCLUSION: ABT plays the central role in PBM, but to achieve the real PBM, there is need to indicate ABT appropriately, according to the individual needs, and use it adequately, without discarding. Our present data reflect the present status of the ABT performance in Japan, and will serve as the basis for the development of strategies to achieve safe and appropriate performance of ABT, and consequently, achieve PBM.

Pilot study of anti-angiogenic vaccine using fixed whole endothelium in patients with progressive malignancy after failure of conventional therapy.

Vaccines targeting tumour angiogenesis were recently shown to inhibit tumour growth in animal models. However, there is still a lack of information about the clinical utility of anti-angiogenic vaccination. Therefore, here, we aimed to test the clinical effects of a vaccine using glutaraldehyde-fixed human umbilical vein endothelial cells (HUVECs). Six patients with recurrent malignant brain tumours and three patients with metastatic colorectal cancer received intradermal injections of 5x10(7) HUVECs/dose (in total 230 vaccinations). ELISA and flow cytometry revealed immunoglobulin response against HUVECs' membrane antigens. ELISPOT and chromium-release cytotoxicity assay revealed a specific cellular immune response against HUVECs, which were lysed in an effectors:targets ratio-dependent manner. Gadolinium-contrasted MRI showed partial or complete tumour responses in three malignant brain tumour patients. Except for a DTH-like skin reaction at the injection site, no adverse effect of vaccination could be observed. Our results suggest that the endothelial vaccine can overcome peripheral tolerance of self-angiogenic antigens in clinical settings, and therefore should be useful for adjuvant immunotherapy of cancer.