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.

  • Original Article
  • Published:

Viral Infections

A survey of allogeneic bone marrow transplant programs in the United States regarding cytomegalovirus prophylaxis and pre-emptive therapy

Bone Marrow Transplantation volume 26, pages 763–767 (2000)Cite this article

Abstract

Despite an extensive literature, no consensus has emerged regarding the optimal preventive strategy for CMV in allogeneic bone marrow transplantation (BMT). No survey of CMV prevention in BMT centers in the United States has yet been published. A questionnaire was sent to all allogeneic BMT programs in the United States, as listed in the November 1998 National Marrow Donor Program (NMDP) address roster. Questions included whether universal prophylaxis, pre-emptive therapy, or some other strategy was used for CMV prevention, and which CMV diagnostic tests were utilized. Eighty-one of 96 programs (86%) responded to the survey. Of these, 46 (56%) utilize a pre-emptive ganciclovir strategy, whereas 17 (21%) utilize universal prophylaxis, and 15 (19%) utilize a hybrid strategy based on risk stratification. The most commonly utilized CMV diagnostic tests are CMV-DNA by PCR (55 centers), shell vial centrifugation culture (52), tissue culture (42), pp65 antigenemia assay (38), and CMV-DNA by Digene hybrid capture (14). Of these, the CMV-DNA by PCR, pp65 antigenemia assay, and shell vial culture are the most frequently utilized as triggers for pre-emptive therapy. Quantitative assays are common (PCR 42%, Digene 64%). We conclude that centers currently performing allogeneic BMT in the United States employ a variety of strategies for CMV prevention, and differ in their diagnostic tests of choice for CMV monitoring. These results emphasize the need for large-scale studies to identify optimal diagnostic and management protocols. Bone Marrow Transplantation (2000) 26, 763–767.

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

Similar content being viewed by others

References

  1. Meyers JD, Flournoy N, Thomas ED . Risk factors for cytomegalovirus infection after human marrow transplantation J Infect Dis 1986 153: 478–488

    Article  CAS  PubMed  Google Scholar 

  2. Schmidt GM . Prophylaxis of cytomegalovirus infection after bone marrow transplantation Semin Oncol 1992 19: (3 Suppl. 7) 20–26

    CAS  PubMed  Google Scholar 

  3. Holland HK, Saral R . Cytomegaloviral virus infection in bone marrow transplantation recipients: strategies for prevention and treatment Support Care Cancer 1993 1: 245–249

    Article  CAS  PubMed  Google Scholar 

  4. Forman SJ, Zaia JA . Treatment and prevention of cytomegalovirus pneumonia after bone marrow transplantation: where do we stand? Blood 1994 83: 2392–2398

    Article  CAS  PubMed  Google Scholar 

  5. Goodrich JM, Boeckh M, Bowden R . Strategies for the prevention of cytomegalovirus disease after marrow transplantation Clin Infect Dis 1994 19: 287–298

    Article  CAS  PubMed  Google Scholar 

  6. Reusser P . The challenge of cytomegalovirus infection after bone marrow transplantation: epidemiology, prophylaxis, and therapy Bone Marrow Transplant 1996 18: (Suppl 2) 107–109

    PubMed  Google Scholar 

  7. Tsinontides AC, Bechtel TP . Cytomegalovirus prophylaxis and treatment following bone marrow transplantation Ann Pharmacother 1996 30: 1277–1290

    Article  CAS  PubMed  Google Scholar 

  8. Prentice HG, Kho P . Clinical strategies for the management of cytomegalovirus infection and disease in allogeneic bone marrow transplantation Bone Marrow Transplant 1997 19: 135–142

    Article  CAS  PubMed  Google Scholar 

  9. Adal KA, Avery RK . Prevention of cytomegalovirus infection after allogeneic bone marrow transplantation. In: Bolwell BJ (ed) Current Controversies in Bone Marrow/Stem Cell Transplantation Humana Press: New Jersey 1999 295–316

    Google Scholar 

  10. Ljungman P . Cytomegalovirus pneumonia: presentation, diagnosis, and treatment Semin Respir Infect 1995 10: 209–215

    CAS  PubMed  Google Scholar 

  11. Riddell SR . Pathogenesis of cytomegalovirus pneumonia in immunocompromised hosts Semin Respir Infect 1995 10: 199–208

    CAS  PubMed  Google Scholar 

  12. Torok-Storb B, Simmons P, Khaira D et al. Cytomegalovirus and marrow function Ann Hematol 1992 64: (Suppl.) A128–131

    Article  PubMed  Google Scholar 

  13. Miller W, Flynn P, McCullough J et al. Cytomegalovirus infection after bone marrow transplantation: an association with acute graft-v-host disease Blood 1986 67: 1162–1167

    Article  CAS  PubMed  Google Scholar 

  14. Emanuel D, Cunninghan I, Jules-Elysee K et al. Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin Ann Intern Med 1988 109: 777–782

    Article  CAS  PubMed  Google Scholar 

  15. Reed EC, Bowden RA, Dandliker PS et al. Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplants Ann Intern Med 1988 109: 783–788

    Article  CAS  PubMed  Google Scholar 

  16. Schmidt GM, Kovacs A, Zaia JA et al. Ganciclovir/immunoglobulin combination therapy for the treatment of human cytomegalovirus-associated interstitial pneumonia in bone marrow allograft recipients Transplantation 1988 46: 905–907

    Article  CAS  PubMed  Google Scholar 

  17. Ljungman P, Engelhard D, Link H et al. Treatment of interstitial pneumonitis due to cytomegalovirus with ganciclovir and intravenous immune globulin: experience of European Bone Marrow Transplant Group Clin Infect Dis 1992 14: 831–835

    Article  CAS  PubMed  Google Scholar 

  18. Husni RN, Gordon SM, Longworth DL et al. Cytomegalovirus infection is a risk factor for invasive aspergillosis in lung transplant recipients Clin Infect Dis 1998 26: 753–755

    Article  CAS  PubMed  Google Scholar 

  19. Meyers JD, Reed EC, Shepp DH et al. Acyclovir for prevention of cytomegalovirus infection and disease after allogeneic bone marrow transplantation New Engl J Med 1988 318: 70–75

    Article  CAS  PubMed  Google Scholar 

  20. Prentice HG, Gluckman E, Powles RP et al. The impact of long-term acyclovir on cytomegalovirus infection and survival in allogeneic bone marrow transplantation Lancet 1994 343: 749–753

    Article  CAS  PubMed  Google Scholar 

  21. Goodrich JM, Bowden RA, Fisher L et al. Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic marrow transplant Ann Intern Med 1993 118: 173–178

    Article  CAS  PubMed  Google Scholar 

  22. Winston DJ, Ho WG, Bartoni RN et al. Ganciclovir prophylaxis of cytomegalovirus infection and disease in allogeneic bone marrow transplant recipients Ann Intern Med 1993 118: 179–184

    Article  CAS  PubMed  Google Scholar 

  23. Salzberger B, Bowden RA, Fackman RC et al. Neutropenia in allogeneic marrow transplant recipients receiving ganciclovir for prevention of cytomegalovirus disease: risk factors and outcome Blood 1997 90: 2502–2508

    Article  CAS  PubMed  Google Scholar 

  24. Li CR, Greenberg PD, Gilbert MJ et al. Recovery of HLA-restricted cytomegalovirus (CMV)-specific T-cell responses after allogeneic bone marrow transplant: correlation with CMV disease and effect of ganciclovir prophylaxis Blood 1994 83: 1971–1979

    Article  CAS  PubMed  Google Scholar 

  25. Goodrich JM, Mori M, Gleaves CA et al. Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation New Engl J Med 1991 325: 1601–1607

    Article  CAS  PubMed  Google Scholar 

  26. Schmidt GM, Horak DA, Niland JC et al. A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants New Engl J Med 1991 324: 1005–1011

    Article  CAS  PubMed  Google Scholar 

  27. Boeckh M, Bowden RA, Goodrich JM et al. Cytomegalovirus antigen detection in peripheral blood leukocytes after allogeneic marrow transplantation Blood 1992 80: 1358–1364

    Article  CAS  PubMed  Google Scholar 

  28. Zaia JA, Schmidt GM Chao NJ et al. Use of preemptive ganciclovir based solely on asymptomatic pulmonary cytomegalovirus infection in marrow transplant recipients – long-term follow-up Blood 1994 84: (10 Suppl. 1) 249a

    Google Scholar 

  29. Einsele H, Enhinger G, Hebart H et al. Polymerase chain reaction monitoring reduces the incidence of cytomegalovirus disease and the duration and side effects of antiviral therapy after bone marrow transplantation Blood 1995 86: 2815–2820

    Article  CAS  PubMed  Google Scholar 

  30. Bacigalupo A, Tedone E, Isaza A et al. CMV-antigenemia after allogeneic bone marrow transplantation: correlation of CMV-antigen positive cell numbers with transplant-related mortality Bone Marrow Transplant 1995 16: 155–161

    CAS  PubMed  Google Scholar 

  31. Boeckh M, Gooley TA, Myerson D et al. Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation – a randomized double-blind study Blood 1996 88: 4063–4071

    Article  CAS  PubMed  Google Scholar 

  32. Mandanas RA, Saez RA, Selby GB, Confer DL . Cytomegalovirus surveillance and prevention in allogeneic bone marrow transplantation: examination of a preemptive plan of ganciclovir therapy Am J Hematol 1996 51: 104–111

    Article  CAS  PubMed  Google Scholar 

  33. Ljungman P, Lore K, Aschan J et al. Use of a semi-quantitative PCR for cytomegalovirus DNA as a basis for pre-emptive antiviral therapy in allogeneic bone marrow transplant patients Bone Marrow Transplant 1996 17: 583–587

    CAS  PubMed  Google Scholar 

  34. Hebart H, Muller C, Loffler J et al. Monitoring of CMV infection: a comparison of PCR from whole blood, plasma-PCR, pp65-antigenemia and virus culture in patients after bone marrow transplantation Bone Marrow Transplant 1996 17: 861–868

    CAS  PubMed  Google Scholar 

  35. Nicholson VA, Whimbey E, Champlin R et al. Comparison of cytomegalovirus antigenemia and shell vial culture in allogeneic marrow transplantation recipients receiving ganciclovir prophylaxis Bone Marrow Transplant 1997 19: 37–41

    Article  CAS  PubMed  Google Scholar 

  36. Boeckh M, Gallez-Hawkins GM, Myerson D et al. Plasma polymerase chain reaction for cytomegalovirus DNA after allogeneic marrow transplantation: comparison with polymerase chain reaction using peripheral blood leukocytes, pp65 antigenemia, and viral culture Transplantation 1997 64: 108–113

    Article  CAS  PubMed  Google Scholar 

  37. Atkinson K, Downs K, Golenia M et al. Prophylactic use of ganciclovir in allogeneic bone marrow transplantation: absence of clinical cytomegalovirus infection Br J Haematol 1991 79: 57–62

    Article  CAS  PubMed  Google Scholar 

  38. Von Bueltzingsloewen A, Bordigoni P, Witz F et al. Prophylactic use of ganciclovir for allogeneic bone marrow transplant recipients Bone Marrow Transplant 1993 12: 197–202

    CAS  PubMed  Google Scholar 

  39. Przepiorka D, Ippoliti C, Panini A et al. Ganciclovir three times per week is not adequate to prevent cytomegalovirus reactivation after T-cell depleted marrow transplant Bone Marrow Transplant 1994 13: 461–464

    CAS  PubMed  Google Scholar 

  40. Verdonck LF, Dekker AW, Rozenberg-Arska M, van den Hoek MR . A risk-adapted approach with a short course of ganciclovir to prevent cytomegalovirus (CMV) pneumonia in CMV-seropositive recipients of allogeneic bone marrow transplants Clin Infect Dis 1997 24: 901–907

    Article  CAS  PubMed  Google Scholar 

  41. Takenaka K, Gondo H, Tanimoto K et al. Increased incidence of cytomegalovirus (CMV) infection and CMV-associated disease after allogeneic bone marrow transplantation from unrelated donors Bone Marrow Transplant 1997 19: 241–248

    Article  CAS  PubMed  Google Scholar 

  42. Boeckh M, Bowden RA, Gooley T et al. Successful modification of a pp65 antigenemia-based early treatment strategy for prevention of cytomegalovirus disease in allogeneic marrow transplant recipients (letter) Blood 1999 93: 1781–1782

    Article  CAS  PubMed  Google Scholar 

  43. Ljungman P, Aschan J, Azinge JN et al. Cytomegalovirus viraemia and specific T-helper cell responses as predictors of disease after allogeneic marrow transplantation Br J Haematol 1993 83: 118–124

    Article  CAS  PubMed  Google Scholar 

  44. Walter EA, Greenberg PD, Gilbert MJ et al. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor New Engl J Med 1995 333: 1038–1044

    Article  CAS  PubMed  Google Scholar 

  45. Ljungman P, DeBock R, Cordonnier C et al. Practices for cytomegalovirus diagnosis, prophylaxis, and treatment in allogeneic bone marrow transplant recipients; a report from the Working Party for Infectious Diseases of the EBMT Bone Marrow Transplant 1993 12: 399–403

    CAS  PubMed  Google Scholar 

  46. Erice A, Chow SW, Biron K et al. Progressive disease due to ganciclovir-resistant cytomegalovirus in immunocompromised patients New Engl J Med 1989 320: 289–293

    Article  CAS  PubMed  Google Scholar 

  47. Reusser P, Cordonnier C, Einsele H et al. European survey of herpesvirus resistance to antiviral drugs in bone marrow transplant recipients Bone Marrow Transplant 1996 17: 813–817

    CAS  PubMed  Google Scholar 

  48. Erice A, Borrell N, Li W et al. Ganciclovir susceptibilities and analysis of UL97 region in cytomegalovirus (CMV) isolates from bone marrow recipients with CMV disease after antiviral prophylaxis J Infect Dis 1998 178: 531–534

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Infectious Disease, Cleveland Clinic Foundation, Cleveland, OH, USA

    RK Avery, KA Adal & DL Longworth

  2. Department of Hematology-Oncology, Cleveland Clinic Foundation, Cleveland, OH, USA

    BJ Bolwell

  3. Department of Transplant Center, Cleveland Clinic Foundation, Cleveland, OH, USA

    RK Avery & BJ Bolwell

Authors
  1. RK Avery
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. KA Adal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. DL Longworth
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. BJ Bolwell
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Avery, R., Adal, K., Longworth, D. et al. A survey of allogeneic bone marrow transplant programs in the United States regarding cytomegalovirus prophylaxis and pre-emptive therapy. Bone Marrow Transplant 26, 763–767 (2000). https://doi.org/10.1038/sj.bmt.1702608

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1702608

Keywords

This article is cited by

Search

Advanced search

Quick links