Supportive Care in Cancer

, Volume 21, Issue 5, pp 1265–1271 | Cite as

Efficacy of prophylactic lamivudine to prevent hepatitis B virus reactivation in B-cell lymphoma treated with rituximab-containing chemotherapy

  • Yin-Hua Wang
  • Lei Fan
  • Li Wang
  • Run Zhang
  • Ji Xu
  • Cheng Fang
  • Jian-Yong Li
  • Wei Xu
Original Article



Reactivation of hepatitis B virus (HBV) is a common complication in patients with HBV infection who receive cytotoxic chemotherapy. In rituximab-containing chemotherapy for B-cell lymphoma, severe hepatitis due to HBV reactivation occurred. The aim of this study is to estimate the effect of prophylactic lamivudine on the risk of HBV reactivation in patients with HBV infection who receive rituximab-containing chemotherapy.


In this study, HBV markers and liver function tests were monitored in 268 consecutive patients with B-cell lymphoma, who received rituximab-containing chemotherapy between January 2008 and November 2011. Sixty-nine patients (25.7 %) with either chronic HBV infection or past HBV infection received prophylaxis with lamivudine 100 mg daily by oral intake.


In the HBsAg-positive group, six (6/38) patients developed hepatitis, only one of which was attributed to HBV reactivation. In the HBsAg-negative and HBcAb-positive group, two (2/31) patients developed hepatitis, none of which was attributed to HBV reactivation.


These results support that prophylactic lamivudine can prevent HBV reactivation for B-cell lymphoma with HBV infection who was receiving rituximab-containing chemotherapy.


Hepatitis B virus Lamivudine Rituximab B-cell lymphoma 


  1. 1.
    Sun Z, Ming L, Zhu X, Lu J (2002) Prevention and control of hepatitis B in China. J Med Virol 67:447–450PubMedCrossRefGoogle Scholar
  2. 2.
    Lau JY, Lai CL, Lin HJ, Lok AS, Liang RH, Wu PC, Chan TK, Todd D (1989) Fatal reactivation of chronic hepatitis B virus infection following withdrawal of chemotherapy in lymphoma patients. Q J Med 73:911–917PubMedGoogle Scholar
  3. 3.
    Nakamura Y, Motokura T, Fujita A, Yamashita T, Ogata E (1996) Severe hepatitis related to chemotherapy in hepatitis B virus carriers with hematologic malignancies. Survey in Japan, 1987–1991. Cancer 78:2210–2215PubMedCrossRefGoogle Scholar
  4. 4.
    Xunrong L, Yan AW, Liang R, Lau GK (2001) Hepatitis B virus (HBV) reactivation after cytotoxic or immunosuppressive therapy–pathogenesis and management. Rev Med Virol 11:287–299PubMedCrossRefGoogle Scholar
  5. 5.
    Galbraith RM, Eddleston AL, Williams R, Zuckerman AJ (1975) Fulminant hepatic failure in leukaemia and choriocarcinoma related to withdrawal of cytotoxic drug therapy. Lancet 2:528–530PubMedCrossRefGoogle Scholar
  6. 6.
    Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242PubMedCrossRefGoogle Scholar
  7. 7.
    van der Kolk LE, Baars JW, Prins MH, van Oers MH (2002) Rituximab treatment results in impaired secondary humoral immune responsiveness. Blood 100:2257–2259PubMedGoogle Scholar
  8. 8.
    Suzan F, Ammor M, Ribrag V (2001) Fatal reactivation of cytomegalovirus infection after use of rituximab for a post-transplantation lymphoproliferative disorder. N Engl J Med 345:1000PubMedCrossRefGoogle Scholar
  9. 9.
    Goldberg SL, Pecora AL, Alter RS, Kroll MS, Rowley SD, Waintraub SE, Imrit K, Preti RA (2002) Unusual viral infections (progressive multifocal leukoencephalopathy and cytomegalovirus disease) after high-dose chemotherapy with autologous blood stem cell rescue and peritransplantation rituximab. Blood 99:1486–1488PubMedCrossRefGoogle Scholar
  10. 10.
    Bermudez A, Marco F, Conde E, Mazo E, Recio M, Zubizarreta A (2000) Fatal visceral varicella-zoster infection following rituximab and chemotherapy treatment in a patient with follicular lymphoma. Haematologica 85:894–895PubMedGoogle Scholar
  11. 11.
    Ng HJ, Lim LC (2001) Fulminant hepatitis B virus reactivation with concomitant listeriosis after fludarabine and rituximab therapy: case report. Ann Hematol 80:549–552PubMedCrossRefGoogle Scholar
  12. 12.
    Tsutsumi Y, Kawamura T, Saitoh S, Yamada M, Obara S, Miura T, Kanamori H, Tanaka J, Asaka M, Imamura M, Masauzi N (2004) Hepatitis B virus reactivation in a case of non-Hodgkin’s lymphoma treated with chemotherapy and rituximab: necessity of prophylaxis for hepatitis B virus reactivation in rituximab therapy. Leuk Lymphoma 45:627–629PubMedCrossRefGoogle Scholar
  13. 13.
    Sera T, Hiasa Y, Michitaka K, Konishi I, Matsuura K, Tokumoto Y, Matsuura B, Kajiwara T, Masumoto T, Horiike N, Onji M (2006) Anti-HBs-positive liver failure due to hepatitis B virus reactivation induced by rituximab. Intern Med 45:721–724PubMedCrossRefGoogle Scholar
  14. 14.
    Dervite I, Hober D, Morel P (2001) Acute hepatitis B in a patient with antibodies to hepatitis B surface antigen who was receiving rituximab. N Engl J Med 344:68–69PubMedCrossRefGoogle Scholar
  15. 15.
    Niscola P, Del Principe MI, Maurillo L, Venditti A, Buccisano F, Piccioni D, Amadori S, Del Poeta G (2005) Fulminant B hepatitis in a surface antigen-negative patient with B-cell chronic lymphocytic leukaemia after rituximab therapy. Leukemia 19:1840–1841PubMedCrossRefGoogle Scholar
  16. 16.
    Cho CH, Hwang WL, Cheng SB, Lee TY, Teng CL (2011) Hepatitis B reactivation induced by rituximab maintenance therapy for lymphoma. Ann Hematol 90:111–112PubMedCrossRefGoogle Scholar
  17. 17.
    Lee IC, Huang YH, Chu CJ, Lee PC, Lin HC, Lee SD (2010) Hepatitis B virus reactivation after 23 months of rituximab-based chemotherapy in an HBsAg-negative, anti-HBs-positive patient with follicular lymphoma. J Chin Med Assoc 73:156–160PubMedCrossRefGoogle Scholar
  18. 18.
    Mimidis K, Tsatalas C, Margaritis D, Martinis G, Spanoudakis E, Kotsiou S, Kartalis G, Bourikas G (2002) Efficacy of lamivudine in patients with hematologic malignancies receiving chemotherapy and precore mutant chronic active hepatitis B. Acta Haematol 107:49–51PubMedCrossRefGoogle Scholar
  19. 19.
    Hamaki T, Kami M, Kusumi E, Ueyama J, Miyakoshi S, Morinaga S, Mutou Y (2001) Prophylaxis of hepatitis B reactivation using lamivudine in a patient receiving rituximab. Am J Hematol 68:292–294PubMedCrossRefGoogle Scholar
  20. 20.
    Kami M, Hamaki T, Murashige N, Kishi Y, Kusumi E, Yuji K, Miyakoshi S, Ueyama J, Morinaga S, Mutou Y (2003) Safety of rituximab in lymphoma patients with hepatitis B or hepatitis C virus infection. Hematol J 4:159–162PubMedCrossRefGoogle Scholar
  21. 21.
    Swerdlow SH, Campo E, Harris NL et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. IARC Press, LyonGoogle Scholar
  22. 22.
    Koo YX, Tan DS, Tan IB, Tao M, Chow WC, Lim ST (2010) Hepatitis B virus reactivation and role of antiviral prophylaxis in lymphoma patients with past hepatitis B virus infection who are receiving chemoimmunotherapy. Cancer 116:115–121PubMedGoogle Scholar
  23. 23.
    Xu W, Miao KR, Zhu DX, Fang C, Zhu HY, Dong HJ, Wang DM, Wu YJ, Qiao C, Li JY (2011) Enhancing the action of rituximab by adding fresh frozen plasma for the treatment of fludarabine refractory chronic lymphocytic leukemia. Int J Cancer 128:2192–2201PubMedCrossRefGoogle Scholar
  24. 24.
    Artz AS, Somerfield MR, Feld JJ, Giusti AF, Kramer BS, Sabichi AL, Zon RT, Wong SL (2010) American Society of Clinical Oncology provisional clinical opinion: chronic hepatitis B virus infection screening in patients receiving cytotoxic chemotherapy for treatment of malignant diseases. J Clin Oncol 28:3199–3202PubMedCrossRefGoogle Scholar
  25. 25.
    Hernandez JA, Diloy R, Salat D, del Rio N, Martinez X, Castellvi JM (2003) Fulminant hepatitis subsequent to reactivation of precore mutant hepatitis B virus in a patient with lymphoma treated with chemotherapy and rituximab. Haematologica 88:ECR22PubMedGoogle Scholar
  26. 26.
    Hsu C, Hsiung CA, Su IJ, Hwang WS, Wang MC, Lin SF, Lin TH, Hsiao HH, Young JH, Chang MC, Liao YM, Li CC, Wu HB, Tien HF, Chao TY, Liu TW, Cheng AL, Chen PJ (2008) A revisit of prophylactic lamivudine for chemotherapy-associated hepatitis B reactivation in non-Hodgkin's lymphoma: a randomized trial. Hepatology 47:844–853PubMedCrossRefGoogle Scholar
  27. 27.
    Kim JS, Hahn JS, Park SY, Kim Y, Park IH, Lee CK, Cheong JW, Lee ST, Min YH (2007) Long-term outcome after prophylactic lamivudine treatment on hepatitis B virus reactivation in non-Hodgkin's lymphoma. Yonsei Med J 48:78–89PubMedCrossRefGoogle Scholar
  28. 28.
    Li YH, He YF, Jiang WQ, Wang FH, Lin XB, Zhang L, Xia ZJ, Sun XF, Huang HQ, Lin TY, He YJ, Guan ZZ (2006) Lamivudine prophylaxis reduces the incidence and severity of hepatitis in hepatitis B virus carriers who receive chemotherapy for lymphoma. Cancer 106:1320–1325PubMedCrossRefGoogle Scholar
  29. 29.
    Takahashi T, Koike T, Hashimoto S, Miura T, Nakamura J, Yamada S, Miura T, Yanagi M, Yamazaki K, Okoshi S, Aoyagi Y (2009) A case of lamivudine-sensitive de novo acute hepatitis B induced by rituximab with the CHOP regimen for diffuse large B cell lymphoma. Hepatol Int 3:316–322PubMedCrossRefGoogle Scholar
  30. 30.
    Dai MS, Chao TY, Kao WY, Shyu RY, Liu TM (2004) Delayed hepatitis B virus reactivation after cessation of preemptive lamivudine in lymphoma patients treated with rituximab plus CHOP. Ann Hematol 83:769–774PubMedCrossRefGoogle Scholar
  31. 31.
    Tsutsumi Y, Tanaka J, Kawamura T, Miura T, Kanamori H, Obara S, Asaka M, Imamura M, Masauzi N (2004) Possible efficacy of lamivudine treatment to prevent hepatitis B virus reactivation due to rituximab therapy in a patient with non-Hodgkin’s lymphoma. Ann Hematol 83:58–60PubMedCrossRefGoogle Scholar
  32. 32.
    He YF, Li YH, Wang FH, Jiang WQ, Xu RH, Sun XF, Xia ZJ, Huang HQ, Lin TY, Zhang L, Bao SP, He YJ, Guan ZZ (2008) The effectiveness of lamivudine in preventing hepatitis B viral reactivation in rituximab-containing regimen for lymphoma. Ann Hematol 87:481–485PubMedCrossRefGoogle Scholar
  33. 33.
    Yeo W, Chan TC, Leung NW, Lam WY, Mo FK, Chu MT, Chan HL, Hui EP, Lei KI, Mok TS, Chan PK (2009) Hepatitis B virus reactivation in lymphoma patients with prior resolved hepatitis B undergoing anticancer therapy with or without rituximab. J Clin Oncol 27:605–611PubMedCrossRefGoogle Scholar
  34. 34.
    Pei SN, Chen CH, Lee CM, Wang MC, Ma MC, Hu TH, Kuo CY (2010) Reactivation of hepatitis B virus following rituximab-based regimens: a serious complication in both HBsAg-positive and HBsAg-negative patients. Ann Hematol 89:255–262PubMedCrossRefGoogle Scholar
  35. 35.
    Wang F, Xu RH, Luo HY, Zhang DS, Jiang WQ, Huang HQ, Sun XF, Xia ZJ, Guan ZZ (2008) Clinical and prognostic analysis of hepatitis B virus infection in diffuse large B-cell lymphoma. BMC Cancer 8:115PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Yin-Hua Wang
    • 1
  • Lei Fan
    • 1
  • Li Wang
    • 1
  • Run Zhang
    • 1
  • Ji Xu
    • 1
  • Cheng Fang
    • 1
  • Jian-Yong Li
    • 1
  • Wei Xu
    • 1
  1. 1.Department of HematologyThe First Affiliated Hospital of Nanjing Medical University, Jiangsu Province HospitalNanjingChina

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