By contrast, HCV serum viral weight increased during the therapy in patient n. two individuals with type II combined cryoglobulinaemia syndrome associated with chronic HCV illness unresponsive to conventional treatments, including restorative plasmapheresis, who have been successfully treated with rituximab in our Haematology Unit. The rituximab treatment experienced a major medical impact in both of these difficult to manage individuals: cutaneous manifestations, including purpura, and peripheral neuropathy improved and corticosteroid requirements were reduced. Individuals and methods We treated two individuals, a 70-12 months old female patient (patient n. 1) and a 60-12 months old male patient (patient n. 2), who had been affected by type II combined cryoglobulinaemia for 7 and 5 years, respectively. Both individuals experienced antibodies to HCV, as determined by enzyme-linked immunosorbent assays (Ortho-Clinical Diagnostics Systems, Raritan, NJ, USA) and by recombinant-based immunoblot assays (Ortho Diagnostic Systems) and were positive for serum HCV RNA by nested polymerase chain reaction (PCR). Over the years they were treated in our Haematology Unit with restorative plasmapheresis associated with corticosteroids, cyclophosphamide and interferon plus ribavirin but these treatments were not tolerated and were, therefore, halted. The patients started treatment with rituximab only. The restorative schedule consisted of a single course of rituximab (Mabthera; Roche, Milan, Italy) given at a dose of 375mg/m2 by intravenous infusion on days +1, +8, +15, and +22, as with the treatment of B-cell lymphoma. Only medium-to low doses of corticosteroids (prednisone 0.5mg/kg/day time) were allowed while concomitant treatment for the type II mixed cryoglobulinaemia, with no further increase in dosage. The individuals were evaluated at baseline and then regular monthly for 6 months. The evaluations consisted of a complete physical exam and laboratory studies, including assessment of: (i) purpura, obtained as +++ (diffuse and prolonged involvement of the trunk and the lower limbs), ++ (diffuse and prolonged involvement of the lower Sstr2 limbs), + (limited or fluctuating involvement of the lower limbs) or 0 (no purpura); (ii) neuropathy, with symptoms graded from 0 to RVX-208 10 relating to a patient-scored visual analogue level, and electromyography of the lower limbs, performed at baseline and repeated after 3 months of rituximab treatment; (iii) lymphoma features, identified on a bone marrow biopsy RVX-208 at baseline, circulation cytometry analysis of lymphoid markers on peripheral blood mononuclear cells at baseline and then regular monthly and on bone marrow mononuclear cells at baseline and after 3 months of treatment; (iv) routine laboratory parameters such as serum liver enzymes, RF, quantification of serum cryoglobulins and of HCV serum viral weight. HCV genotyping was carried out as previously explained and serum HCV RNA was quantified before and after treatment (at RVX-208 baseline and at weeks +3 and +6) by quantitative PCR (TAQMAN, Roche Diagnostics, Basel, Switzerland). Results Both patients completed the full course of rituximab RVX-208 therapy and experienced good reactions (Table I). Purpura disappeared within one month in one patient and within 2 weeks in the additional. Symptoms of peripheral neuropathy improved in both individuals; however, electromyographic findings at month +3 were unchanged with respect to those at baseline. As regards lymphoma features, depletion of CD20+ peripheral blood B cells was achieved by month RVX-208 +1 and managed until month +6 in both individuals. In contrast, in the bone marrow there was a reduction of only 25%. Serum levels of RF and cryoglobulins decreased, while aminotransferase levels, normal at baseline, remained within the normal ranges. By contrast, HCV serum viral weight increased during the therapy in individual n. 2 and then decreased to the previous value later on; there were minimal fluctuations in patient 1. Corticosteroid treatment was no longer required by either individual and was, therefore, 1st reduced and then suspended shortly after the start of rituximab therapy. Rituximab appeared to be well-tolerated by both individuals and was not associated with small or major adverse events such as serious infections. In the long-term, both individuals relapsed after interruption of therapy at month +6 and month +12, with recurrence of cutaneous manifestations and neuropathic symptoms related to combined cryoglobulinaemia leading us to re-treat the individuals obtaining the same results. Table I Results thead th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Patient n. 1 /th th align=”remaining” valign=”top” rowspan=”1″ colspan=”1″ Clinical status /th th align=”center” valign=”top”.