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Regression of Low-Grade Non-Hodgkin's Lymphoma After Treatment With Pegylated Interferon Plus Ribavirin in Hepatitis C Virus Infection

Department of Internal Medicine, Azienda Ospedaliera "Santa Maria degli Angeli"—Pordenone, Pordenone; and Division of Medical Oncology A, National Cancer Institute, Aviano, Italy

Michele Spina, Umberto Tirelli

Division of Medical Oncology A, National Cancer Institute, Aviano, Italy

To the Editor:

The report by Vallisa et al¹ provides important additional evidence about the possible role of antiviral therapy for hepatitis C virus (HCV) infection in the treatment of patients with HCV-related low-grade B-cell non-Hodgkin's lymphoma (B-NHL).

The authors report complete hematologic responses and loss of HCV-RNA in seven of 13 patients with low-grade B-NHL and HCV infection after treatment with pegylated interferon and ribavirin. In 11 of these 13 patients, a molecular study was performed, but only two patients showed loss of the monoclonal immunoglobulin gene component.

In 1996, we reported complete remission of low-grade B-NHL (lymphoplasmocystic or lymphoplasmocytoid immunocytomas) in three patients with type II mixed cryoglobulinemia and HCV infection after treatment with interferon alone.² Remission was also associated with the loss of detectable HCV-RNA and with a complete regression of the monoclonal B-cell component in peripheral-blood mononuclear cells. These findings were subsequently confirmed in some series,³ but not in others.⁴

In addition, we were able to genotype the HCV and found that all of the patients who had no response to antiviral therapy or had relapsed had genotype 1b.

Nevertheless, from 2002 to 2003 we treated three patients with chronic HCV infections and indolent low-grade non-Hodgkin's lymphoma (histology, plasmocytoid), with pegylated interferon alfa-2b (PEG-INTRON; Schering-Plough, Kenilworth, NJ) 80 µg subcutaneously once a week and ribavirin 1,000 mg (REBETOL; Schering-Plough) orally daily. Treatment was scheduled for 12 months. In two of these three patients, HCV infection was associated with type II mixed cryoglobulinemia.

One of the three patients treated with pegylated interferon and ribavirin obtained complete lymphoma remission after HCV eradication, one patient showed a partial response, and one patient did not show a response.

The patient who responsed to the antiviral treatment had a complete disappearance of all clinical manifestations of the disease (purpura, arthralgias, and weakness) and a reduction of the serum cryocrit level. Follow-up of this patient at 11 months showed maintenance of complete remission of B-NHL and HCV-RNA.

Taking our data into consideration, it would be of interest to know some additional information from the Vallisa et al series, in particular, the type of cryoglobulins observed in these patients, the presence of symptoms related to the presence of cryoglobulins, and the cryoglobulins' relationship to the response to the treatment.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Vallisa D, Bernuzzi P, Arcaini L, et al: Role of anti-hepatitis C virus (HCV) treatment in HCV-related, low-grade, B-cell, non-Hodgkin's lymphoma: A multicenter Italian experience. J Clin Oncol 23:468-473, 2005[Abstract/Free Full Text]

2. Mazzaro C, Franzin F, Tulissi P, et al: Regression of monoclonal B cell expansion in patients affected by mixed cryoglobulinemia responsive to -interferon therapy. Cancer 77:2604-2613, 1996[CrossRef][Medline]

3. Zuchermann E, Zuchermann T, Sahar D, et al: The effect of anti-viral therapy on t(14;18) translocation and immunoglobulin gene rearrangement in patients with chronic hepatitis C virus infection. Blood 97:1555-1559, 2001[Abstract/Free Full Text]

4. Hermine O, Lefrere F, Bronowicki JP, et al: Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 347:89-94, 2002[Abstract/Free Full Text]

Related Reply

• In Reply:
  Daniele Vallisa, Patrizia Bernuzzi, Antonio Lazzaro, Elena Trabacchi, Elisa Anselmi, Anna Lisa Arcari, Carlo Moroni, Raffaella Bertè, and Luigi Cavanna
  JCO 2005 23: 4471 [Full Text]

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