Hepatitis B Virus Reactivation in Lymphoma Patients With Prior Resolved Hepatitis B Undergoing Anticancer Therapy With or Without Rituximab

• Published in: Journal of clinical oncology Vol. 27; no. 4; pp. 605 - 611
• Main Authors: Yeo, Winnie, Chan, Tung C., Leung, Nancy W.Y., Lam, Wai Y., Mo, Frankie K.F., Chu, Miu Ting, Chan, Henry L.Y., Hui, Edwin P., Lei, Kenny I.K., Mok, Tony S.K., Chan, Paul K.S.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 01.02.2009
• Subjects: Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - analysis; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cyclophosphamide - therapeutic use; Doxorubicin - therapeutic use; Hematologic and hematopoietic diseases; Hepatitis B Surface Antigens - blood; Hepatitis B virus - physiology; Hepatitis B, Chronic - virology; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Large B-Cell, Diffuse - drug therapy; Male; Medical sciences; Middle Aged; Prednisolone - therapeutic use; Rituximab; Tumors; Vincristine - therapeutic use; Virus Activation; Antineoplastic agent; Human; Reactivation; Orthohepadnavirus; Rituximab; Hepatic disease; Malignant hemopathy; Monoclonal antibody; Lymphoid neoplasm; Lymphoma; Infection; Virus; Viral hepatitis B; Cancerology; Treatment; Hepadnaviridae; Lymphoproliferative syndrome; Viral disease; Immunotherapy; Digestive diseases; Hepatitis B virus; Cancer
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2008.18.0182

Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication in cancer patients with chronic HBV (hepatitis B surface antigen [HBsAg] positive) undergoing cytotoxic chemotherapy. In patients who have resolved HBV (HBsAg negative and antibody to hepatitis B core antigen [anti-HBc] +/- antibody to hepatitis B surface antigen [anti-HBs] positive), such incidence has been much less common until recent use of rituximab. In this study on HBsAg-negative/anti-HBc-positive lymphoma patients, the objectives were to determine the HBV reactivation rate in patients treated with rituximab-containing chemotherapy and to compare it with the rate in patients treated without rituximab. Between January 2003 and December 2006, all patients diagnosed with CD20(+) diffuse large B-cell lymphoma (DLBCL) had HBsAg determined before anticancer therapy. They were treated with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or rituximab plus CHOP (R-CHOP). HBsAg-negative patients had anti-HBc determined; serum was stored for anti-HBs and HBV DNA. All patients were observed for HBV reactivation, which was defined as detectable HBV DNA with ALT elevation during and for 6 months after anticancer therapy. Among 104 CD20(+) DLBCL patients, 80 were HBsAg negative. Of the latter, 46 patients (44.2%) were HBsAg negative/anti-HBc positive; 25 of these patients were treated with CHOP, and none had HBV reactivation. In contrast, among the 21 patients treated with R-CHOP, five developed HBV reactivation, including one patient who died of hepatic failure (P = .0148). Exploratory analysis identified male sex, absence of anti-HBs, and use of rituximab to be predictive of HBV reactivation. Among HBsAg-negative/anti-HBc-positive DLBCL patients treated with R-CHOP, 25% developed HBV reactivation. Close monitoring until at least 6 months after anticancer therapy is required, with an alternative approach of prophylactic antiviral therapy to prevent this potentially fatal condition.