Correspondence
Treatment of HCV-Related Mantle-Cell Lymphoma with Ribavirin and Pegylated Interferon Alfa
N Engl J Med 2003; 349:2078-2079November 20, 2003
- Article
To the Editor:
We expand on the data presented by Hermine et al., who demonstrated the antitumor efficacy of interferon alfa in hepatitis C virus (HCV)–infected patients with marginal-zone lymphoma.1 We report the details of anti-HCV therapy in the patient from whom we established a B lymphoma cell line that is persistently infected with HCV.2 In culture, the line continuously produces HCV, which can infect primary human hepatocytes, peripheral-blood mononuclear cells, and Raji cells.
In 1995, this patient, a 66-year-old man, was found to have cryoglobulinemia, with elevated levels of rheumatoid factor and creatinine. Antibody to HCV was present; the levels of liver enzymes were normal. A computed tomographic (CT) scan revealed splenomegaly. Bone marrow biopsy revealed mantle-cell lymphoma, marked immunophenotypically with monoclonal lambda light chains, and coexpression of CD20 and CD5. The initial treatment was given six months later, when diffuse colonic involvement was documented. The patient received chlorambucil, resulting in a complete remission of two years' duration, followed by a Bcl-1–positive relapse in the middle portion of the transverse colon. Repeated therapy with chlorambucil was ineffective; splenectomy was performed.
The spleen was extensively involved by lymphoma, which was similar morphologically to that seen in prior biopsy specimens, with expression of Bcl-1 and CD20; CD23 and CD5 were not detected. Two distinct abnormal clones were detected on karyotyping: t(11;14) in 8 of 20 cells and trisomy 12 in 2 of 20 cells. Immunoglobulin heavy-chain gene rearrangement without class switching was shown, without evidence of t(14;18) or bcl-2 rearrangement. Splenic tissue was used for establishment of the cell line.2
The patient received rituximab but had another relapse, after which he received seven cycles of fludarabine, mitoxantrone, and rituximab, without a response. With an HCV load above 1 million copies per milliliter, he was begun on ribavirin (400 mg given orally, twice a day) and pegylated interferon alfa (150 μg given subcutaneously every week), on November 2, 2001. Within one month, the HCV load was undetectable, and it has remained so. Anti-HCV therapy was stopped on July 31, 2002. Repeated positron-emission tomographic scanning, CT scanning, and colonoscopy (in July 2003) revealed no evidence of lymphoma.
In contrast to the current case, Hermine et al. presented no information to indicate that their patients actually harbored HCV within lymphoma cells.1 Furthermore, whereas their patients had splenic marginal-zone lymphoma, therapy against HCV was effective in this case of HCV-associated mantle-cell lymphoma. The pathological spectrum of B-cell neoplasia reported in association with HCV is broad.3 The successful treatment of HCV-related mantle-cell lymphoma with ribivarin and interferon alfa suggests that this therapeutic approach should be studied in all types of B-cell lymphoma associated with HCV.
3 ReferencesAlexandra M. Levine, M.D.
Shigetaka Shimodaira, M.D.
Michael M.C. Lai, M.D., Ph.D.
University of Southern California Keck School of Medicine, Los Angeles, CA 90033
hornor@usc.edu 1
Hermine O ,Lefrere F ,Bronowicki J-P , et al. Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med 2002;347:89-94
Full Text | Web of Science | Medline2
Sung VMH ,Shimodaira S ,Doughty A , et al. Establishment of B-cell lymphoma cell lines persistently infected with hepatitis C virus in vivo and in vitro: the apoptotic effects of virus infection. J Virol 2003;77:2134-2146
CrossRef | Web of Science | Medline3
Zuckerman E ,Zuckerman T ,Levine AM , et al. Hepatitis C virus infection in patients with B-cell non-Hodgkin lymphoma. Ann Intern Med 1997;127:423-428
Web of Science | Medline
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