Clinical usefulness of cell-free and concentrated ascites reinfusion therapy (CART) in combination with chemotherapy for malignant ascites: a post-marketing surveillance study.

BACKGROUND: Cell-free and concentrated ascites reinfusion therapy (CART) has been suggested to be able to treat malignant ascites more safely and effectively with chemotherapy because of its ability to retain serum protein and albumin. Although the characteristics of cancer types and CART and the clinical implications of combination therapy with antitumor agents are becoming widespread, there are limited reports on its efficacy and complications. METHODS: In this prospective observational national post-marketing study, 128 patients with malignancies received 300 CART sessions at 22 centers. After excluding other malignancies, the patients were divided into four groups: gynecological malignancies with chemotherapy (GYC+; 18 cases and 36 times) and without chemotherapy (GYC-; 35 cases and 52 times), and gastrointestinal malignancies with chemotherapy (GIC+; 8 cases and 16 times) and without chemotherapy (20 cases and 58 times). RESULTS: There were significant reductions in the body weight in all groups and significant reductions in abdominal circumference and significant improvements in the diet and Eastern Cooperative Oncology Group performance status only in the GYC+ group. The total serum protein and albumin increased significantly in all groups, except for the GIC+ group, before and after CART. There was no significant difference in the presence or absence of antitumor medication. CONCLUSION: With CART, there were differences in the improvement of the clinical symptoms between malignancy groups. The combination of CART and antineoplastic agents may be as safe as CART alone in cases of exudative malignant ascites.

Safety and efficacy of cell-free and concentrated ascites reinfusion therapy (CART) in refractory ascites: Post-marketing surveillance results.

We performed post-marketing surveillance to evaluate the safety and efficacy of cell-free and concentrated ascites reinfusion therapy (CART). In total, 356 CART sessions in 147 patients at 22 centers were performed. The most common primary disease was cancer (128 cases, 300 sessions). Mean amount of ascites collected was 3.7 L, and mean concentration ratio was 9.2. Mean amount of reinfused protein was 67.8 g (recovery rate, 72.0%). Performance status, dietary intake, urine volume, body weight and abdominal circumference were significantly improved after CART. Body temperature increased significantly, by 0.3°C on average. Concomitant steroids and/or NSAIDs use before reinfusion was significantly and negatively associated with increases in body temperature. Most adverse events were fever and chills. This study examined a large number of patients compared with previous studies, and showed that CART is an effective and relatively safe treatment for refractory ascites, such as malignant ascites.

Selective adsorption of human CD4 T cells.

The pathogenesis of most autoimmune diseases directly involves CD4(+) helper T cells. To remove CD4(+) T cells selectively from the circulation, we designed a new column in which an anti-CD4 monoclonal antibody was immobilized on the activated substance. Nearly 90% of CD4(+) T cells were selectively adsorbed from whole blood with a single passage through the column in vitro, resulting in depletion of the antigen-specific T cell responses. We conclude that this new column would be potentially useful for treatment of T cell-mediated autoimmune diseases.

Cytapheresis with a filter for selective removal of CD4+ T cells in experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a major animal model of human multiple sclerosis (MS). CD4+ T cells are thought to play a pivotal role in the pathogenesis of EAE and MS. In order to investigate the depletion of CD4+ T cells from the systemic circulation as an effective strategy for the treatment of MS, we performed extracorporeal CD4+ T cell adsorption, using a filter to which anti-CD4+ antibody is immobilized as a ligand, in adoptively transferred EAE. Rats treated with CD4+ T cell removal filter (CD4RF) exhibited milder clinical signs of EAE and earlier recovery than those receiving sham treatment. Moreover, the thymic cells from EAE rats treated with CD4RF exhibited a suppressed proliferative response and IFN-gamma production to myelin basic protein. These results suggest that depletion of CD4+ T cells from the systemic circulation by extracorporeal treatment is a potentially useful strategy for treatment of acute phase and relapsing MS.

Development of a device for selective removal of CD4+ T cells.

To control antigen (Ag)-specific immune cells is important in the treatment of autoimmune diseases. In particular, controlling the immune response of autoimmune T cells is effective in the treatment of these diseases. The development of a device that can remove CD4+ T cells specifically by extracorporeal circulation is now in progress, with the aim to deplete autoimmune T cells. We developed a removal material made of polypropylene non-woven fabrics with anti human CD4 monoclonal antibody immobilized on the surface. Using a column packed with the removal material, we succeeded in removing CD4+ T cells specifically from peripheral whole blood by direct perfusion. Moreover, CD4+ T cells can be specifically removed even from blood with lower surface antigen density by in vitro activation.