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Safety of hematopoietic stem cell transplantation from hepatitis B core antibodies-positive donors with low/undetectable viremia in HBV-naïve children

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Abstract

Scarce data exist on allogeneic hematopoietic stem cell transplantation (HSCT) outcomes in hepatitis B virus (HBV)-naïve recipients from HBV-experienced donors. Long-term follow-up is herein reported for 17 allogeneic HSCT performed in 13 HBV-naïve children from HBc-antibodies-positive donors between 2006 and 2012. Four donors were HBs-antigen-positive, with detectable but low viremia in 2 cases (<2 log10IU/ml). HBV-DNA was undetectable in all transplanted cell products. Recipients’ HBV prophylaxis consisted of pre-transplant vaccination, polyvalent immune globulins, specific anti-HBV immune globulins, and/or oral lamivudine in 3, 12, 8, and 8 children, respectively. No case of HBV transmission occurred based on negative close monitoring of recipients’ HBV serology and plasma HBV-DNA during a median follow-up of 22 months. In case of undetectable viremia in the donor, prophylaxis with vaccination and/or immune globulins in the recipient seems to be sufficient and lamivudine prophylaxis might be unnecessary to prevent viral transmission. In case of undetectable viremia in the donor, a systematic screening of HBV DNA in the stem cell product might be unnecessary to confirm the low risk of viral transmission. Prior exposure to HBV in the donor should not be considered a contraindication to HSCT.

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References

  1. Romet-Lemonne JL, McLane MF, Elfassi E, Haseltine WA, Azocar J, Essex M (1983) Hepatitis B virus infection in cultured human lymphoblastoid cells. Science 221:667–669

    Article  CAS  PubMed  Google Scholar 

  2. Zeldis JB, Mugishima H, Steinberg HN, Nir E, Gale RP (1986) In vitro hepatitis B virus infection of human bone marrow cells. J Clin Invest 78:411–417

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Mason A, Yoffe B, Noonan C, Mearns M, Campbell C, Kelley A, Perrillo RP (1992) Hepatitis B virus DNA in peripheral-blood mononuclear cells in chronic hepatitis B after HBsAg clearance. Hepatology 16:36–41

    Article  CAS  PubMed  Google Scholar 

  4. Ma R, Xing Q, Shao L, Wang D, Hao Q, Li X, Sai L, Ma L (2011) Hepatitis B virus infection and replication in human bone marrow mesenchymal stem cells. Virol J 8:486

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Lau GK, Lie AK, Kwong YL, Lee CK, Hou J, Lau YL, Lim WL, Liang R (2000) A case-controlled study on the use of HBsAg-positive donors for allogeneic hematopoietic cell transplantation. Blood 96:452–458

    CAS  PubMed  Google Scholar 

  6. Locasciulli A, Alberti A, Bandini G, Polchi P, Arcese W, Alessandrino P, Bosi A, Testa M, Bacigalupo A; on the behalf of GITMO (1995) Allogeneic bone marrow transplantation from HBsAg+ donors: a multicenter study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Blood 86:3236–3240

    CAS  PubMed  Google Scholar 

  7. Locasciulli A, Testa M, Valsecchi MG, Bacigalupo A, Solinas S, Tomas JF, Ljungman P, Alberti A (1999) The role of hepatitis C and B virus infections as risk factors for severe liver complications following allogeneic BMT: a prospective study by the Infectious Disease Working Party of the European Blood and Marrow Transplantation Group. Transplantation 68:1486–1491

    Article  CAS  PubMed  Google Scholar 

  8. Hui CK, Lie A, Au WY, Ma SY, Leung YH, Zhang HY, Sun J, Cheung WWW, Chim CS, Kwong YL, Liang R, Lau GKK (2005) Effectiveness of prophylactic Anti-HBV therapy in allogeneic hematopoietic stem cell transplantation with HBsAg positive donors. Am J Transplant 5:1437–1445

    Article  CAS  PubMed  Google Scholar 

  9. Ustün C, Koç H, Karayalcin S, Akyol G, Gürman G, Ilhan O, Akan H, Ozcan M, Arslan O, Konuk N, Uysal A, Beksaç M (1997) Hepatitis B virus infection in allogeneic bone marrow transplantation. Bone Marrow Transplant 20:289–296

    Article  PubMed  Google Scholar 

  10. Tomblyn M, Chen M, Kukreja M, Aljurf MD, Al Mohareb F, Bolwell BJ, Cahn JY, Carabasi MH, Gale RP, Gress RE, Gupta V, Hale GA, Ljungman P, Maziarz RT, Storek J, Wingard JR, Young JAH, Horowitz MM, Ballen KK (2012) No increased mortality from donor or recipient hepatitis B- and/or hepatitis C-positive serostatus after related-donor allogeneic hematopoietic cell transplantation. Transpl Infect Dis 14:468–478

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Strasser SI, McDonald GB (1999) Hepatitis viruses and hematopoietic cell transplantation: A guide to patient and donor management. Blood 93:1127–1136

    CAS  PubMed  Google Scholar 

  12. Liang R (2009) How I treat and monitor viral hepatitis B infection in patients receiving intensive immunosuppressive therapies or undergoing hematopoietic stem cell transplantation. Blood 113:3147–3153

    Article  CAS  PubMed  Google Scholar 

  13. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, Wingard JR, Young JAH, Boeckh MJ; Center for International Blood and Marrow Research; National Marrow Donor program; European Blood and MarrowTransplant Group; American Society of Blood and Marrow Transplantation; Canadian Blood and Marrow Transplant Group; Infectious Diseases Society of America; Society for Healthcare Epidemiology of America; Association of Medical Microbiology and Infectious Disease Canada; Centers for Disease Control and Prevention (2009) Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 15:1143–1238

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Yu M, Ward Y, Poirier MC, Olivero OA (2009) Centrosome amplification induced by the antiretroviral nucleoside reverse transcriptase inhibitors lamivudine, stavudine, and didanosine. Environ Mol Mutagen 50:718–724

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Wutzler P, Thust R (2001) Genetic risks of antiviral nucleoside analogues—a survey. Antiviral Res 49:55–74

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank L. Dal Cortivo (Biotherapy Laboratory, Necker Children’s Hospital, Paris) for the technical assistance, C. Rouzioux (Virology Laboratory, Necker Children’s Hospital, Paris), M. Debré, M. Chomton, and G. Cros (Pediatric Immuno-hematology Unit, Necker Children’s Hospital, Paris) for the continuous helpful discussions.

Conflict of interest

PF received grants from the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) (to his institution) and from SIDACTION. M-LC received grants from the French ANRS (to her institution) and from JANNSEN for board membership. AF received grants from the European Research Council (ERC PIDIMMUN no. 249816) (to his institution). For the remaining authors: no commercial or other association that might pose a conflict of interest.

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Authors and Affiliations

  1. Pediatric Immuno-hematology Unit, Assistance Publique–Hôpitaux de Paris (AP-HP), Necker Children’s Hospital, Paris, France

    P. Frange, B. Neven, D. Moshous, F. Touzot, S. Heritier, M. Cavazzana, J.-L. Casanova, A. Fischer & S. Blanche

  2. University Paris Descartes, Sorbonne Paris Cité, EA3620, Paris, France

    P. Frange, M. Leruez-Ville, M.-L. Chaix & S. Blanche

  3. Virology Laboratory, Assistance Publique–Hôpitaux de Paris (AP-HP), Necker Children’s Hospital, Paris, France

    M. Leruez-Ville, L. Mascard & M.-L. Chaix

  4. University Paris Descartes, Sorbonne Paris Cité, IMAGINE Institute, Paris, France

    B. Neven, D. Moshous, F. Touzot, S. Heritier, M. Cavazzana, J.-L. Casanova, A. Fischer & S. Blanche

  5. INSERM U768, Paris, France

    B. Neven, D. Moshous, F. Touzot, M. Cavazzana & A. Fischer

  6. Biotherapy Department, Assistance Publique–Hôpitaux de Paris (AP-HP), Necker Children’s Hospital, Paris, France

    F. Touzot & M. Cavazzana

  7. Laboratory of Human Genetics of Infectious Diseases, INSERM U980, Paris, France

    J.-L. Casanova

  8. St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, USA

    J.-L. Casanova

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  1. P. Frange
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  2. M. Leruez-Ville
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  3. B. Neven
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  4. L. Mascard
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  5. D. Moshous
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  6. F. Touzot
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  7. S. Heritier
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  8. M.-L. Chaix
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  9. M. Cavazzana
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  10. J.-L. Casanova
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  11. A. Fischer
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  12. S. Blanche
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Correspondence to P. Frange.

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Frange, P., Leruez-Ville, M., Neven, B. et al. Safety of hematopoietic stem cell transplantation from hepatitis B core antibodies-positive donors with low/undetectable viremia in HBV-naïve children. Eur J Clin Microbiol Infect Dis 33, 545–550 (2014). https://doi.org/10.1007/s10096-013-1982-x

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  • DOI: https://doi.org/10.1007/s10096-013-1982-x

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