Annals of Hematology

, Volume 83, Issue 12, pp 769–774 | Cite as

Delayed hepatitis B virus reactivation after cessation of preemptive lamivudine in lymphoma patients treated with rituximab plus CHOP

  • Ming-Shen Dai
  • Tsu-Yi Chao
  • Woei-Yau Kao
  • Rong-Yaun Shyu
  • Tan-Mei Liu
Original Article

Abstract

Preemptive lamivudine in lymphoma patients undergoing intensive chemotherapy can effectively prevent chemotherapy-related HBV reactivation. Nevertheless, the safety profile after withdrawal of lamivudine and the impact of rituximab-containing chemotherapy on HBV reactivation has not been defined. To illustrate the necessity of prolonged surveillance after cessation of preemptive lamivudine in lymphoma patients treated with rituximab and chemotherapy, four patients with B-cell NHL carrying HBV received rituximab plus CHOP. Preemptive lamivudine therapy was administered 1 week before chemotherapy until 4 weeks after completion of chemotherapy. Serial serum alanine aminotransferase (ALT), total bilirubin, and HBV-DNA levels were prospectively monitored in three patients. The fourth patient was closely monitored for ALT. The HBV DNA was checked after development of clinical overt hepatitis. The peripheral blood CD20+ B-lymphocyte counts were analyzed periodically in two patients. All of the three patients studied prospectively had virological relapses with surgence of HBV DNA 6–8 months after completion of rituximab-plus-CHOP (R+CHOP) therapy. Two of the three patients had biochemical relapses and one of them developed severe hepatitis. Sequencing for HBV polymerase gene in these patients failed to show evident emergence of lamivudine-resistant mutations. The fourth patient developed a hepatitis flare-up 6 months after completion of chemotherapy. The CD20+ lymphocytes were totally depleted when HBV DNA started to increase. Delayed HBV reactivation can occur in lymphoma patients receiving R+CHOP after withdrawal of preemptive lamivudine. More protracted lamivudine therapy may be an alternative to close monitoring following chemotherapy, and further studies are needed to define optimal duration of lamivudine therapy.

Keywords

HBV reactivation Lamivudine Lymphoma Preemptive treatment Rituximab 

References

  1. 1.
    Lok AS, Liang RH, Chiu EK, Wong KL, Chan TK, Todd D (1991) Reactivation of hepatitis B virus replication in patients receiving cytotoxic therapy: report of a prospective study. Gastroenterology 100:182–188Google Scholar
  2. 2.
    Liang R, Lau GKK, Kwong YL (1999) Chemotherapy and bone marrow transplantation for cancer patients who are also chronic hepatitis B carriers: a review of the problem. J Clin Oncol 17:394–398PubMedGoogle Scholar
  3. 3.
    Cheng AL, Hsiung CA, Su IJ, Chen PJ, Chang MC, Tsao CJ, Kao WY, Uen WC, Hsu CH, Tien HF, Chao TY, Chen LT, Whang-Peng J (2003) A prospective randomized study comparing steroid-containing versus steroid-free chemotherapy in the treatment of hepatitis B virus carriers with malignant lymphoma. Hepatology 37:1320–1328CrossRefPubMedGoogle Scholar
  4. 4.
    Leaw SJ, Yen CJ, Huang WT, Chen TY, Su WC, Tsao CJ (2004) Preemptive use of interferon or lamivudine for hepatitis B reactivation in patients with aggressive lymphoma receiving chemotherapy. Ann Hematol 5:270–275CrossRefGoogle Scholar
  5. 5.
    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 346:235–242CrossRefPubMedGoogle Scholar
  6. 6.
    Kolk LE, Baars JW, Prins MH, Oers MHJ (2002) Rituximab treatment results in impaired secondary humoral immune responsiveness. Blood 100:2257–2259PubMedGoogle Scholar
  7. 7.
    Lau GKK, Yiu HHY, Fong DYT, Cheng HC, Au WY, Lai LSF, Cheung M, Zhang HY, Lie A, Ngan R, Liang R (2003) Early is superior to deferred preemptive lamivudine therapy for hepatitis B patients undergoing chemotherapy. Gastroenterology 125:1742–1749PubMedGoogle Scholar
  8. 8.
    Yeo W, Chan PK, Hui P, Ho WM, Lam KC, Kwan WH, Zhong S, Johnson PJ (2003) Hepatitis B virus reactivation in breast cancer patients receiving cytotoxic chemotherapy: a prospective study. J Med Virol 70:553–561CrossRefPubMedGoogle Scholar
  9. 9.
    Rossi G, Pelizzari A, Motta M, Puoti M (2001) Primary prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HBsAg carriers with lymphoid malignancies treated with chemotherapy. Br J Haematol 115:58–62CrossRefPubMedGoogle Scholar
  10. 10.
    Hoonkoop P, Man RA, Niesters HGM, Zondervan PE, Schalm SW (2000) Acute exacerbation of chronic hepatitis B virus infection after withdrawal of lamivudine therapy. Hepatology 32:635–639CrossRefPubMedGoogle Scholar
  11. 11.
    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 344:68–69CrossRefGoogle Scholar
  12. 12.
    Westhoff TH, Jochimsen F, Schmittel A, Stoffler-Meilicke M, Schafer JH, Zidek W, Gerlich WH, Thiel E (2003) Fatal hepatitis B virus reactivation by an escape mutant following rituximab therapy. Blood 102:1930CrossRefPubMedGoogle Scholar
  13. 13.
    Suzan F, Ammor M, Ribrag (2001) Fatal reactivation of cytomegalovirus infection after use of rituximab for a post-transplantation lymphoproliferative disorder. N Engl J Med 345:1000CrossRefGoogle Scholar
  14. 14.
    Sharma VR, Fleming DR, Slone SP (2000) Pure red cell aplasia due to parvovirus B19 in a patients treated with rituximab. Blood 96:1184–1186PubMedGoogle Scholar
  15. 15.
    Lazdina U, Alheim M, Nyström J, Hultgren C, Borisova G, Sominskaya I, Pumpens P, Peterson DL, Milich DR, Sällberg M (2003) Priming of cytotoxic T cell resonses to exogenous hepatitis B virus core antigen is B cell dependent. J Gen Virol 84:139–141CrossRefPubMedGoogle Scholar
  16. 16.
    Czuczman MS, Grillo-Lopez AJ, White CA, Saleh M, Gordon L, LoBuglio AF, Jonas C, Klippenstein D, Dallaire B, Varns C (1999) Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol 17:268–276PubMedGoogle Scholar
  17. 17.
    Ng H, Lim L (2001) Fulminant hepatitis B virus reactivation with concomitant listeriosis after fludarabine and rituximab therapy. Ann Hematol 80:549–552CrossRefPubMedGoogle Scholar
  18. 18.
    Skrabs C, Muller C, Agis H, Mannhalter C, Jager U (2002) Treatment of HBV-carrying lymphoma patients with rituximab and CHOP: a diagnostic and therapeutic challenge. Leukemia 16:1884–1886CrossRefPubMedGoogle Scholar
  19. 19.
    Hernández JA, Diloy R, Salat D, del Río N, Martínez X, Castellví 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:(06)ECR22Google Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Ming-Shen Dai
    • 1
  • Tsu-Yi Chao
    • 1
  • Woei-Yau Kao
    • 1
  • Rong-Yaun Shyu
    • 2
  • Tan-Mei Liu
    • 3
  1. 1.Division of Hematology/Oncology, Department of Medicine, Tri-Service General HospitalNational Defense Medical CenterTaipeiTaiwan ROC
  2. 2.Division of Gastroenterology, Department of Medicine, Tri-Service General HospitalNational Defense Medical CenterTaipeiTaiwan ROC
  3. 3.Division of Rheumatology and Immunology, Department of Medicine, Tri-Service General HospitalNational Defense Medical CenterTaipeiTaiwan ROC

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