Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

HBV reactivation after hematopoietic stem cell transplantation and rituximab-containing chemotherapy: a 12-year experience at a single center

Bone Marrow Transplantation volume 54, pages 629–631 (2019)Cite this article

Subjects

We recently reported hepatitis B virus (HBV) reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in our 11-year experience [1]. HBV reactivation is also a well-known complication in patients receiving autologous HSCT (auto-HSCT) and Rituximab plus corticosteroid-containing chemotherapy (R-steroid-chemo) [2]; however, no comparative study has been performed for the rate of HBV reactivation among three major treatment groups. A retrospective review of using a computer database was performed for patients with resolved HBV infection who underwent allo-HSCT, auto-HSCT, and R-steroid-chemo between January 2005 and December 2016. Patients were identified as having a resolved HBV infection if they were hepatitis B s antigen (HBsAg)-negative, hepatitis B core antibody (anti-HBc)-, and/or hepatitis B s antibody (anti-HBs)-positive. No patient had been vaccinated for HBV before or after therapy. Patients who had not been followed up for at least 6 months were excluded from this study. The outcome data for each patient were censored at the end of follow-up or death. The patients with resolved HBV infection were also subsequently tested for the HBV viral load and assessed for HBV reactivation after allo-HSCT, auto-HSCT, and R-steroid-chemo. HBV reactivation was defined as the development of positive HBV DNA and/or HBsAg. The study protocol complied with the Good Clinical Practice Guidelines and the 1975 Declaration of Helsinki, and was approved by the office for Human Research Studies at Hamanomachi Hospital. Measurements of HBsAg, anti-HBs, anti-HBc, and HBV DNA were carried out as described before [1]. The cumulative incidence of HBV reactivation was calculated using the Kaplan–Meier method and the difference was evaluated by the log-rank test. A value of P < 0.05 was considered to be statistically significant. Statistical analyses were performed using the SPSS statistics software package, version 23.0 (SPSS Inc., Chicago, IL, USA).

Of the 139 patients who underwent auto-HSCT during the study period, 32 had evidence of a resolved HBV infection. Of them, four patients were excluded because of death or transfer to another hospital within 6 months, and 3 were excluded because allo-HSCT was performed after auto-HSCT. One patient was an HCV carrier. This left 24 patients ultimately enrolled in this study. The median age was 60 years (range: 37–73) and 14 (58%) were men. The median anti-HBc level at the baseline was 2.95 IU/l (range: < 1.0–10.2). Nine patients (37%) were negative ( < 1.0 S/CO) for anti-HBc but positive for anti-HBs. In contrast, six patients (25%) were negative for anti-HBs but positive for anti-HBc. During the study period, 4 of the 24 patients (16.7%) developed post-HSCT HBV reactivation. The median interval between auto-HSCT and the development of HBV reactivation was 255 days (range: 220–777). The cumulative rates of HBV reactivation after auto-HSCT at 1, 3, and 5 years were 12.5%, 17.6%, and 17.6%, respectively (Fig. 1).

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

References

  1. Bae SK, Gushima T, Saito N, Yamanaka I, Shimokawa T, Matsuo Y, et al. The impact of hepatitis B core antibody levels on HBV reactivation after allogeneic hematopoietic SCT: an 11-year experience at a single center. Bone Marrow Transplant. 2016;51:1496–8.

    Article  CAS  Google Scholar 

  2. Sarmati L, Andreoni M, Antonelli G, Arcese W, Bruno R, Coppola N, et al. Recommendations for screening, monitoring, prevention, prophylaxis and therapy of hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation—a position paper. Clin Microbiol Infect. 2017;23:935–40.

    Article  CAS  Google Scholar 

  3. Kempinska A, Kwak EJ, Angel JB. Reactivation of hepatitis B infection following allogeneic bone marrow transplantation in a hepatitis B-immune patient: case report and review of the literature. Clin Infect Dis. 2005;41:1277–82.

    Article  Google Scholar 

  4. Hammond SP, Borchelt AM, Ukomadu C, Ho VT, Baden LR, Marty FM. Hepatitis B virus reactivation following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2009;15:1049–59.

    Article  Google Scholar 

  5. de Koning C, Plantinga M, Besseling P, Boelens JJ, Nierkens S. Immune reconstitution after allogeneic hematopoietic cell transplantation in children. Biol Blood Marrow Transplant. 2016;22:195–206.

    Article  Google Scholar 

  6. Uhm JE, Kim K, Lim TK, Park B-B, Park S, Hong YS, et al. Changes in serologic markers of hepatitis B following autologous hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2007;13:463–8.

    Article  CAS  Google Scholar 

  7. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348:2609–17.

    Article  CAS  Google Scholar 

  8. Tanaka H, Sakuma I, Hashimoto S, Takeda Y, Sakai S, Takagi T, et al. Hepatitis B reactivation in a multiple myeloma patient with resolved hepatitis B infection during bortezomib therapy: case report. J Clin Exp Hematop. 2012;52:67–9.

    Article  Google Scholar 

  9. Goldberg R, Smith E, Bell S, Thompson A, Desmond PV. Bortezomib monotherapy in patients with multiple myeloma is associated with reactivation of hepatitis B. Intern Med J. 2013;43:835–6.

    Article  CAS  Google Scholar 

  10. Kusumoto S, Tanaka Y, Suzuki R, Watanabe T, Nakata M, Takasaki H, et al. Monitoring of hepatitis B virus (HBV) DNA and risk of HBV reactivation in B-cell lymphoma: a prospective observational study. Clin Infect Dis. 2015;61:719–29.

    Article  CAS  Google Scholar 

  11. Garcia-Rodriguez MJ, Canales MA, Hernandez-Maraver D, Hernandez-Navarro F. Late reactivation of resolved hepatitis B virus infection: an increasing complication post rituximab-based regimens treatment? Am J Hematol. 2008;83:673–5.

    Article  CAS  Google Scholar 

  12. Zoppoli G, Gabriele Z, Bruzzone B, Bianca B, Caligiuri P, Patrizia C, et al. From a medical mistake to a clinical warning: the case of HBV mutant virus reactivation in haematological patients. Br J Haematol. 2009;144:969–70.

    Article  Google Scholar 

  13. Koo YX, Tay M, Teh YE, Teng D, Tan DSW, Tan IBH, et al. Risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen negative/hepatitis B core antibody positive patients receiving rituximab-containing combination chemotherapy without routine antiviral prophylaxis. Ann Hematol. 2011;90:1219–23.

    Article  CAS  Google Scholar 

  14. Hwang JP, Lok AS-F. Management of patients with hepatitis B who require immunosuppressive therapy. Nat Rev Gastroenterol Hepatol. 2014;11:209–19.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to Megumi Naganuma for her valuable support in the preparation of this manuscript.

Financial disclosure

None to declare.

Author information

Authors and Affiliations

  1. The Center for Liver Disease, Hamanomachi Hospital, 3-3-1 Nagahama, Chuo-ku, Fukuoka, 810-8539, Japan

    Sung Kwan Bae, Toshifumi Gushima & Kazuhiro Takahashi

  2. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan

    Noriyuki Saito, Ikumi Yamanaka, Yayoi Matsuo, Shuro Yoshida, Ichiro Kawano, Hideho Henzan & Tetsuya Eto

  3. Medicine and Biosystemic Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Shinji Shimoda

Authors
  1. Sung Kwan Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toshifumi Gushima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Noriyuki Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ikumi Yamanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yayoi Matsuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shuro Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ichiro Kawano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hideho Henzan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shinji Shimoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tetsuya Eto
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kazuhiro Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sung Kwan Bae.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bae, S.K., Gushima, T., Saito, N. et al. HBV reactivation after hematopoietic stem cell transplantation and rituximab-containing chemotherapy: a 12-year experience at a single center. Bone Marrow Transplant 54, 629–631 (2019). https://doi.org/10.1038/s41409-018-0355-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-018-0355-6

Search

Advanced search

Quick links