Frontline antiviral therapy in a series of HCV-related low grade non-Hodgkin lymphoma

Background. The association between HCV infection and type II crioglobulinemia or B-cell non-Hodgkin lymphoma (NHL) suggested its role in clonal B cell proliferation. The regression of NHL after antiviral treatment could be an indirect evidence of this pathogenetic hypothesis. Aim.We have treated 5 patients, affected by low grade B-cell NHL (LG-NHL), with different clinical presentations, with antiviral therapy alone with pegylated interferon (PegIFN) and ribavirin (Rbv) in order to evaluate the hematological response in respect of viral response. Methods. From 2005 to 2009, 5 patients, affected by LG- NHL at diagnosis have been treated by only antiviral therapy with PegIFN and Rbv (PegIFNa2a 180 mcg weekly, Rbv 800-1000 mg daily) for 6 months (4 pts) or 12 months (1 pt). M/F ratio was 4/1; the mean age was 57.2 years (range 51-73). HCV infection was diagnosed by means of HCVRNA poliymerase chain reaction (3 cases with genotype 2 and 2 with 1b), before in 4 pts and concomitant in 1 patient, at lymphoma diagnosis. Only one patient has already received other combinations of antiviral therapy in the past. The study included 2 marginal zone lymphoma (MZL), 2 not otherwise specified LG-NHL and 1 lymphplasmacytic lymphoma/ Waldenstrom macroglobulinemia (LPL). The two marginal zone lymphomas showed bone marrow involvement, one with abdominal nodes, bilateral orbital mass and sub cutaneous lesions, the other with splenomegaly, thoracic and abdominal nodes and peripheral B cell clone. The two LG-NHL showed in one case only multiple liver lesions, in the other the patient presented with splenomegaly, a modest bone marrow involvement and a peripheral B cell clone (CD5, CD10 and CD43 negative). The case of LPL presented with splenomegaly, bone marrow involvement and carried a serum monoclonal component IgMk. No patients presented nor B symptom neither bulky disease. Results. All five patients completed the planned treatment course. Sustained virologic response (SVR) was achieved in four patients. Hematologic re-staging at the end of antiviral therapy, demonstrated that, among the four patients that gained a SVR, 3 had a CR and one had a PR. The patient that obtained only a reduction of viremia was in hematologic PR. The treatment was well tolerated; only one patients presented a hematologic toxicity grade I WHO, and needed erithropoietine support. After a mean follow up of 14.6 months from the end of therapy (range 1-27), three patients are still in CR and maintain SVR, two patients are in PR; interestingly one patient in SVR, presents a progressive reduction of monoclonal component and splenomegaly. Conclusion. Although the limited number of patients involved, the study demonstrates that antiviral therapy could be considered as frontline therapeutic option in a subset of HCV-related LG-NHL, confirming the important role of HCV chronic stimulation in lymphomagenesis. The relationship between SVR and hematologic response is impressive and, in 1 patient, the quality of PR improved during the follow-up.