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Objective The objective of this review was to define a core set of recommendations for the treatment of HCV-associated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion. Methods Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements. Results An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild–moderate HCV-related MCS. Prolonged treatment (up to 72 weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low–medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild–moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A low-antigen-content diet can be considered as supportive treatment in all symptomatic MCS patients. Although there are no data from controlled trials, controlling pain should always be attempted by tailoring the treatment to individual patients on the basis of the guidelines used in other vasculitides. Conclusion Although there are few controlled randomised trials of MCS treatment, increasing knowledge of its pathogenesis is opening up new frontiers. The recommendations provided may be useful as provisional guidelines for the management of MCS.

Cryoglobulinemic Syn&come (CS) is a multi-systemic disease, and its fatal evolution can involve different organs. Aims: To describe the most frequent causes of death in CS, by researching different evolutions between older cases and those of the last 15 years. Patients: The data of 238 patients affected by symptomatic cryoglobulinemia followed by our Medicine Department in the last 30 years are recorded in a database. 54 are presently living and being followed, 70 (36F, 34M) have died. The type II/type III ratio is 5/4. We distinguish between two groups, the oldest, without any data on HCV, and the most recent who were tested for HCV. The follow-up ranges from 0.5 to 16 years. Results: Liver diseases (25 cases, 9 with hepatic carcinomas), lymphomas and myeloproliferative diseases (12), and cardiovascular events (8) are the most reported causes of death. Sepsis, neurological syndromes, nephropathy, other malignancies and diffuse vasculitis are also reported. The median age at death was 67.2 years (58.4 in the oldest group, 71.9 in the other). Hepatic carcinomas are reported only after 1991. Conclusion: Cirrhosis complications are more frequent in patients affected by HCV. The increase in instrumental diagnostic ability and the improved survival of patients with cirrhosis account for the increase in patients with hepatic carcinomas. Improved treatment has resulted in a reduction of deaths from renal failure.

The recognition of effector cell populations that are able to actively form conjugates with target cells is of major importance in studies of lymphocyte cytotoxicity. A number of methodologies have been described to identify the conjugates and count them, but there have been few studies of the birding capability of the different subsets of effector cells involved in the conjugation phenomenon. Here we describe a methodology that permits the study of two surface markers on lymphocytes conjugated to K562 target cells. In particular, the expression of low density CD8 (CD8 dim ) has been studied on both CD3 + and CD16 + lymphocytes bound to K562 target cells. Previously described methodologies, either optical microscopy or flow cytometry, were not able to identify the effector population by mAb double staining, especially in the case of antigens expressed at low density. The flow cytometric methodology described here permits the measurement of the binding activity of small lymphocyte subsets such as the CD3 + 8 dim+ population. However, the method could be used to study the binding activity of any effector population defined by mAb double staining.

Summary Background In an attempt to mobilise peripheral blood progenitor cells (PBPC) from patients with breast cancer, Epirubicin supported with G-CSF was tested. Another aim of the study was also to optimize the procedure so that the number of leukapheresis procedures could be reduced. These cells were subsequently reinfused as hematologic rescue after high-dose chemotherapy programs. Patients and methods Twenty-nine patients received Epirubicin 150 mg/sqm + G-CSF at the dose of 5 μg/kg/bw s.c. daily, starting 24 hours after chemotherapy. Twelve had metastatic, eight inflammatory or locally advanced disease, and nine were treated in an adjuvant setting. Results The median numbers of CD34+ cells and CFU-GM collected were 12.9 × 10Vkg/bw and 111.7 × 104/kg/bw, respectively. The mean number of leukapheresis procedures per patient was 1.8 ±0.3 (range 1–3), and the mean day of the first procedure was the tenth ± 1 (range 8–13) after Epirubicin. The minimum required target for one high-dose procedure was collected in a single leukapheresis in 13 patients. Moreover, in 9 cases one procedure was adequate for two high-dose courses (i.e. >10 × 10Vkg/bw CD34+ cells). Response to Epirubicin was evaluable in 14/20 cases, with a response rate of 50%. Conclusions Epirubicin delivered at 150 mg/sqm is a very effective mobilising agent for breast cancer patients; to ameliorate the response rate other active drug(s) should be added.