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Journal of Clinical Oncology, Vol 26, No 15 (May 20), 2008: pp. 2584-2586 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.15.4807
Rituximab-Induced Hepatitis C Virus Reactivation After Spontaneous Remission in Diffuse Large B-Cell LymphomaDivision of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan A 68-year-old man had been suffering from a mass on the left side of his neck for 2 months. He underwent biopsy at another other hospital, and diffuse large B-cell lymphoma (Fig 1A) was diagnosed, with positive results for CD20 (Fig 1B), CD10, and bcl-6. Therefore, he was referred to our hospital for further treatment. Systemic work-up was arranged, and computed tomography scan showed an 82 x 62 mm mass over the left supraclavicular area with retroperitoneal lymphadenopathy. According to the examination, the lymphoma stage was stage IIIA, with an International Prognostic Index score of 3 (elevated lactate dehydrogenase, advanced age, and stage). A hepatitis C virus (HCV) antibody test was positive. By then, neither abnormal liver function nor liver cirrhosis was discovered. Chemotherapy with the standard dosage of cyclophosphamide, mitoxantrone, vincristine, and prednisolone (CNOP) was commenced on October 27, 2005. After the first cycle of chemotherapy, no major complications developed. Thus we arranged the next cycle of CNOP accompanied with rituximab on November 22, 2005. However, the patient's ALT and AST levels increased rapidly (Fig 2). Also, HCV RNA increased to 5.6 x 106/mL. Subsequent cycles of chemotherapy were withheld because of slow recovery of liver function, which gradually returned to normal 6 months later. Meanwhile, the patient's neck mass continued to shrink day after day despite lack of further chemotherapy. The follow-up computed tomography scan on January 20, 2006, revealed marked decrease in the size of the original lesion (Fig 3A and 3B). HCV RNA count on May 17, 2006, was less than 100/mL. No further impaired liver function has been detected since June 2006. Until October 2007, no evidence of recurrent malignant lymphoma for the patient was noted through regular surveillance (Fig 4A and 4B).
Hepatitis B reactivation after chemotherapy has been well documented.1 However, chemotherapy-induced hepatitis C reactivation in diffuse large B-cell lymphoma is relatively rare. In a retrospective study, the incidence of liver function impairment in HCV-infected patients who underwent chemotherapy to treat diffuse large B-cell lymphoma was higher.2 In this study, most patients completed their therapeutic courses without interruption because liver injuries were usually mild, from grade 1 to grade 2. Only rare cases were reported to develop severe hepatitis after conventional chemotherapy.3 Rituximab, an anti-CD20 agent, mainly inhibits B-cell function. Many cases of hepatitis B reactivation were observed when administering rituximab to treat diffuse large B-cell lymphoma.4 A case report showed that an HCV-positive patient receiving rituximab treatment had increased HCV RNA without liver dysfunction.5 One previous study monitoring HCV RNA and liver function after rituximab combination therapy disclosed that one of five patients had severe liver dysfunction accompanied by slightly increased HCV RNA, and these patients’ outcome was relatively poor.6 Another study showed that HCV-infected patients have a higher incidence of malignant lymphoma.7 Several researchers reported that treating hepatitis C with interferon resulted in disappearance of indolent lymphoma.8 However, the prognosis of the HCV-positive patients with diffuse large B-cell is still controversial.2,9 No liver function deterioration was noted after the first cycle of chemotherapy in this patient. However, after rituximab was added to the chemotherapeutic regimen, his ALT and AST elevated promptly. Importantly, synchronized increment of HCV RNA was detected. The result provided a clue regarding the relationship between hepatitis C reactivation and the use of rituximab. Contrary to the prior study, this patient experienced complete response of malignant lymphoma after recovery from liver injury. The duration of disease-free survival has lasted for more than 1 year. Further investigation is needed to disclose the association of HCV reactivation and the prognosis of lymphoma. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES 1. Coiffier B: Hepatitis B virus reactivation in patients receiving chemotherapy for cancer treatment: Role of Lamivudine prophylaxis. Cancer Invest 24:548-552, 2006[CrossRef][Medline] 2. Visco C, Arcaini L, Brusamolino E, et al: Distinctive natural history in hepatitis C virus positive diffuse large B-cell lymphoma: Analysis of 156 patients from northern Italy. Ann Oncol 17:1434-1440, 2006 3. Vento S, Cainelli F, Mirandola F, et al: Fulminant hepatitis on withdrawal of chemotherapy in carriers of hepatitis C virus. Lancet 347:92-93, 1996[CrossRef][Medline] 4. Tsutsumi Y, Kanamori H, Mori A, et al: Reactivation of hepatitis B virus with rituximab. Expert Opin Drug Saf 4:599-608, 2005[CrossRef][Medline] 5. Aksoy S, Abali H, Kilickap S, et al: Accelerated hepatitis C virus replication with rituximab treatment in a non-Hodgkin's lymphoma patient. Clin Lab Haematol 28:211-214, 2006[CrossRef][Medline] 6. Ennishi D, Terui Y, Yokoyama M, et al: Monitoring serum hepatitis C virus (HCV) RNA in patients with HCV-infected CD20-positive B-cell lymphoma undergoing rituximab combination chemotherapy. Am J Hematol 83:59-62, 2008[CrossRef][Medline] 7. Mele A, Pulsoni A, Bianco E, et al: Hepatitis C virus and B-cell non-Hodgkin lymphomas: An Italian multi- center case-control study. Blood 102:996-999, 2003 8. 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 9. Besson C, Canioni D, Lepage E, et al: Characteristics and outcome of diffuse large B-cell lymphoma in hepatitis C virus-positive in LNH 93 and LNH 98 Groupe d'Etude des Lymphomas de l'Adulte Programs. J Clin Oncol 24:953-960, 2006 Related Correspondence
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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