The aim of this study was to evaluate the efficacy and safety of interferon-a (IFN-a) therapy of chronic hepatitis B, C and D (HBV, HCV and HDV, respectively) in renal transplant recipients. A group of 42 patients (30 males, 12 females, mean age 38 years) with documented viraemia and chronic active hepatitis (CAH) were studied, of whom 1 had HBV infection alone, 11 had HCV infection alone, 3 had HBV and HDV infection concomitantly, 12 had HBV and HCV infection concomitantly, and 2 had HBV, HCV and HDV infection concomitantly. Patients received 3 MU IFNa three times weekly for 6 months. After IFN-a therapy, 18 patients (43 %) achieved normal alanine aminotransferase (ALT) activity and a partial response was observed in 12 (29%) patients. Two patients relapsed (one with HCV and one with HBV + HCV infection) immediately after the cessation of IFN-a therapy. Repeated liver biopsy was performed in 16 patients after 6-24 months of therapy and revealed progression to cirrhosis in five patients, remission in two and stable disease in nine. None o f the patients cleared HCV RNA, four patients cleared HBeAg (two also HDV), and one both HBV and HCV Five patients died during IFN-a therapy (one as a consequence of liver failure), and four died during the 6 months after therapy (two as a consequence of liver failure). During IFN-a therapy renal allograft function remained stable in 31 patients and acute rejection episodes occurred in 7, of whom 5 lost their graft and all had experienced rejection episodes before. In 16 patients normalization of ALT continued during long-term follow-up (median 22 months, range 0-84 months). IFN-a seemed to be moderately effective in the treatment of chronic HBV or HCV infections, but cannot be recommended for recipients infected with both HBV and HCV.

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Multiple myeloma (MM) remains incurable despite the use of high-dose chemotherapy and stem cell transplantation. However, immunotherapy is expected to offer long-term disease control, or even possibly a cure. We have previously demonstrated the suppressive effect of a recombinant adenovirus carrying human wild-type p53, granulocyte-macrophage colony-stimulating factor, and B7-1 genes (Ad-p53/GM-CSF/B7-1) on the growth of laryngeal cancer cells. In the present study, we evaluated the effects of an Ad-p53/GM-CSF/B7-1-modified myeloma cell vaccine strategy aimed to induce apoptosis and to augment the immunogenicity of MM cells. Both MM cell lines and purified primary myeloma cells were infected with Ad-p53/GM-CSF/B7-1. High expression levels of these three genes were confirmed separately by Western blot, enzyme-linked immunosorbent assay (ELISA), and flow cytometry. When wild-type p53, GM-CSF and B7-1 genes were introduced, the growth of MM cells was inhibited via enhanced apoptosis and the immunogenicity of tumor cells was augmented. The combinatorial effect of these three genes on inducing cytotoxic T lymphocytes (CTLs) was more evident than that of p53 individually or any combinations of two (p53 plus GM-CSF or p53 plus B7-1). Furthermore, significant proliferation of autologous peripheral blood lymphocytes (PBLs) and specific cytotoxicity against autologous primary MM cells were induced in vitro. These results suggest that myeloma cell vaccination co-transferred with p53, GM-CSF and B7-1 genes may be a promising immunotherapeutic approach against MM.

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