The treatment of HCV-associated lymphomas does not differ substantially from that of "idiopathic" B-cell NHL (97). However, the occurrence in the same subject of chronic viral infection and cancer and, in some cases, of other HCV-related disorders may be a conditioning factor for an optimal therapeutic strategy (Fig. 3). In all patients with B-cell NHL the detection of HCV-related markers (anti-HCV and HCV RNA) is obviously mandatory, together with histologic classification and staging of the disease. Before the treatment and during the patient's clinical follow-up, in HCV-positive NHL patients should be carefully evaluated for chronic hepatitis, cirrhosis, hepatocellular carcinoma, mixed cryoglobulinemia syndrome, and other HCV-related disorders, such as thyroiditis and glomerulonephritis. To date, there is not sufficient information on specific complications of cancer chemotherapy in HCV-positive NHL. In a series of patients with lymphoplasmocytoid lymphoma/immunocytoma, the presence or absence of HCV infection did not affect the overall survival of the disease, although the quality of life was significantly worse in HCV-positive individuals regardless the therapeutic interventions (72,78). These differences were mainly related to one or more manifestations of to HCV infection, such as chronic hepatitis, glomerulonephritis, or cryoglobu-linemic vasculitis.
For isolated B-cell NHL, a standard treatment can be followed according to clinical and pathologic assessment of the disease (97). In the presence of severe liver and/or renal impairment, some precautions should be followed to tailor the treatment for the individual patient. In patients with MC complicated by B-cell NHL, but without severe visceral organ involvement, chemotherapy is usually well tolerated and an improvement of cryoglobulinemic syndrome may also be observed. In MC with low-grade NHL, cycles of single-agent (cyclophosphamide) therapy are often sufficient for a complete remission. In HCV-infected individuals, with or without MC, a low-grade NHL can be observed at bone marrow biopsy examination. This is often a clinically
asymptomatic, nonprogressive lymphoma that may not require any specific treatment (Fig. 3).
Following the positive results observed in HCV-related chronic hepatitis (98), an attempt for HCV eradication with combined a-interferon and ribavirin treatment might also be tried in HCV-associated NHL, particularly with low-grade lymphomas (Fig. 3).
With the rapid growth of molecular biology we can hopefully try new and more efficient therapeutic strategies. The recent identification of the interaction between HCV envelope protein E2 and CD81 on both hepatocytes and lymphocytes (99) suggests the possibility of interfering with HCV binding to target cells. A vaccine-based therapy with recombinant HCV proteins may be able to prevent the evolution from viral infection to life-threatening clinical complications.
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