Objective: The objective of this review was to define a core set of recommendations for the treatment of HCVassociated 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 lowantigencontent 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.

Frequently, the number of circulating tumor cells (CTC) isolated in 7.5 mL of blood is too small to reliably determine tumor heterogeneity and to be representative as a "liquid biopsy". In the EU FP7 program CTCTrap, we aimed to validate and optimize the recently introduced Diagnostic LeukApheresis (DLA) to screen liters of blood. Here we present the results obtained from 34 metastatic cancer patients subjected to DLA in the participating institutions. About 7.5 mL blood processed with CellSearch® was used as "gold standard" reference. DLAs were obtained from 22 metastatic prostate and 12 metastatic breast cancer patients at four different institutions without any noticeable side effects. DLA samples were prepared and processed with different analysis techniques. Processing DLA using CellSearch resulted in a 0-32 fold increase in CTC yield compared to processing 7.5 mL blood. Filtration of DLA through 5 μm pores microsieves was accompanied by large CTC losses. Leukocyte depletion of 18 mL followed by CellSearch yielded an increase of the number of CTC but a relative decrease in yield (37%) versus CellSearch DLA. In four out of seven patients with 0 CTC detected in 7.5 mL of blood, CTC were detected in DLA (range 1-4 CTC). The CTC obtained through DLA enables molecular characterization of the tumor. CTC enrichment technologies however still need to be improved to isolate all the CTC present in the DLA.

Acute GVHD (aGVHD) is a major cause of morbidity and mortality after unrelated BMT (UBMT). Our purpose was to analyze the role of extracorporeal photochemotherapy (ECP) in controlling grade II-IV aGVHD in children given UBMT. Of 41 consecutive children, 31 developed grade II-IV aGVHD after UBMT: 16 had a good response to steroids (GR group), whereas 15 underwent ECP (ECP group) within 100 days of UBMT. Eligibility criteria for starting ECP were steroid resistance, dependence or viral reactivations. Criteria for judging response to aGVHD treatment were that the resolution of all signs were considered a complete response (CR), at least a 50% improvement was classified as a partial response (PR) and stable or progressive disease was judged as no response (NR). On completing ECP, the CR rate was 73%, whereas the GR group had a CR rate of 56% by day 100. The 2-year overall survival and progression-free survival rates were 57 and 67% in the GR group vs 85 and 87% in the ECP group. Our data seem to suggest that ECP may improve outcome in patients after UBMT. These findings need to be confirmed in a larger population.

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Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk.