Annals of Hematology

, Volume 64, Supplement 1, pp A152–A157 | Cite as

Prevention of viral infections after bone marrow transplantation

  • U. Schuler
  • G. Ehninger
Article
  • 17 Downloads

Summary

After bone marrow transplantation, a number of viral infections contribute to the morbidity and mortality of the procedure. Established preventive measures to avoid primary infection and reactivation of herpes- and cytomegaloviruses are outlined. Possible future strategies against these viruses (e. g., monoclonal antibodies, transfer of T-lymphocytes) and the possible role of improved diagnostic tools are briefly discussed.

Key words

Bone marrow transplantation Viral infections Cytomegalovirus Immunoglobulins acyclovir Gancyclovir 

References

  1. 1.
    Apperley JF, Goldman JM (1988) Cytomegalovirus: biology, clinical features and methods for diagnosis. Bone Marrow Transplant 3: 253–264Google Scholar
  2. 2.
    Apperley JF, Rice SJ, Bishop JA, Chia YC, Gardner SD, Goldman JM (1986) Late-onset haemorrhagic cystitis after allogeneic BMT is associated with urinary excretion of papovaviridae. Bone Marrow Transplant [Suppl 1]: 52Google Scholar
  3. 3.
    Arseniev L, Battmer K, Andres J, Poliwoda H, Stangel W, Link H (1991) Influence of the leucocyte filtration on the cytomegalovirus DNA content of cellular blood products. EBMT Congress, Cortina D'Ampezzo: 31 (Abstract)Google Scholar
  4. 4.
    Arthur RR, Beckmann AM, Li CC, Saral R, Shah KV (1985) Direct detection of the human papovavirus BK in urine of bone marrow transplant recipients: comparison of DNA hybridization with ELISA. J Med Virol 16: 29–36Google Scholar
  5. 5.
    Atkinson K, Downs K, Golenia M, Biggs J, Marshall G, Dodds A, Concannon A (1991) Prophylactic use of gancyclovir in allogeneic bone marrow transplantation: absence of clinical cytomegalovirus infection. Br J Haematol 79: 57–62Google Scholar
  6. 6.
    Aulitzky WE, Schulz TF, Tilg H, Niederwieser D, Larcher K, Ostberg L, Scriba M, Martindale J, Stern AC, Grass P (1991) Human monoclonal antibodies neutralizing cytomegalovirus (CMV) for prophylaxis of CMV disease: report of a phase I trial in bone marrow transplant recipients. J Infect Dis 163: 1344–1347Google Scholar
  7. 7.
    Bordigoni P, Janot C, Aymard JP, Witz F, Bene MC, Legras B, Schoonemann F, Olive D, Streiff F (1987) Clinical and biological evaluation of the preventive role of anticytomegalovirusspecific immunoglobulins in bone marrow grafts. Randomized study of 60 patients. Nouv Rev Fr Hematol 29: 289–293Google Scholar
  8. 8.
    Bowden RA, Sayers M, Flournoy N, Newton B, Banaji M, Thomas ED, Meyers JD (1986) Cytomegalovirus immune globulin and seronegative blood products to prevent primary cytomegalovirus infection after marrow transplantation. N Engl J Med 314: 1006–1010Google Scholar
  9. 9.
    Bowden RA, Day LM, Amos DE, Meyers JD (1987) Natural cytotoxic activity against cytomegalovirus-infected target cells following marrow transplantation. Transplantation 44: 504–508Google Scholar
  10. 10.
    Bowden RA, Sayers MH, Cays M, Slicher SJ (1989) The role of blood product filtration in the prevention of transfusion-associated cytomegalovirus (CMV) infection after bone marrow transplant. Transfusion 29 [Suppl]: S205 (Abstract)Google Scholar
  11. 11.
    Bowden RA, Fisher LD, Rogers K, Cays M, Meyers JD (1991) Cytomegalovirus (CMV)-specific intravenous immunoglobulin for the prevention of primary CMV-specific infection and disease after marrow transplant. J Infect Dis 164: 483–487Google Scholar
  12. 12.
    Bowden RA, Slichter SJ, Sayers MH, Mori M, Cays MJ, Meyers JD (1991) Use of leukocyte-depleted platelets and cytomegalovirus-seronegative red blood cells for prevention of primary cytomegalovirus infection after marrow transplant. Blood 78: 246–250Google Scholar
  13. 13.
    Bron D, Lagneaux L, Delforge A, Otte C, Snoeck R, Stryckmans P (1991) Prevention of CMV-induced myelosuppression by anti-CMV antibodies: an in vitro model. Exp Hematol 19: 132–135Google Scholar
  14. 14.
    Chapman C, Flower AJ, Durrant ST (1991) The use of vidarabine in the treatment of human polyomavirus-associated acute haemorrhagic cystitis. Bone Marrow Transplant 7: 481–483Google Scholar
  15. 15.
    Condie RM, O'Reilly RJ (1982) Prophylaxis of CMV infection in bone marrow transplant recipients by hyperimmune CMV gamma-globulin. Dev Biol Stand 52: 501–513Google Scholar
  16. 16.
    Condie RM, O'Reilly RJ (1984) Prevention of cytomegalovirus infection by prophylaxis with an intravenous, hyperimmune, native, unmodified cytomegalovirus globulin. Randomized trial in bone marrow transplant recipients. Am J Med 76: 134–141Google Scholar
  17. 17.
    Cottler-Fox M, Lynch M, Pickle LW, Cahill R, Spitzer TR, Deeg HJ (1991) Some but not all benefits of intravenous immunoglobulin therapy after marrow transplantation appear to correlate with IgG trough levels. Bone Marrow Transplant 8: 27–33Google Scholar
  18. 18.
    Crawford DH, Mulholland N, Iliescu V, Hawkins R, Powles R (1986) Epstein-Barr virus infection and immunity in bone marrow transplant recipients. Transplantation 42: 5050–5454Google Scholar
  19. 19.
    De Witte T, Schattenberg A, Van Dijk BA, Galama J, Olthuis H, Van der Meer JW, Kunst VA (1990) Prevention of primary cytomegalovirus infection after allogeneic bone marrow transplantation by using leukocyte-poor random blood products from cytomegalovirus-unscreened blood-bank donors. Transplantation 50: 964–968Google Scholar
  20. 20.
    Drobyski WR, Gottlieb M, Carrigan D, Ostberg L, Grebenau M, Schran H, Magid P, Ehrlich P, Nadler PI, Ash RC (1991) Phase-I study of safety and pharmacokinetics of a human anticytomegalovirus monoclonal antibody in allogeneic bone marrow transplant recipients. Transplantation 51: 1190–1196Google Scholar
  21. 21.
    Drobyski WR, Knox KK, Carrigan DR, Ash RC (1991) Foscarnet therapy of gancyclovir-resistant cytomegalovirus in marrow transplantation. Transplantation 52: 155–157Google Scholar
  22. 22.
    Ehninger G, Vallbracht A, Schuch K, Kumbier I, Dopfer R, Schmidt H, Ostendorf P (1986) Oral prophylaxis of herpes infections using acyclovir following bone marrow transplantation: a clinical and clinico-pharmacological study. Klin Wochenschr 64: 570–574Google Scholar
  23. 23.
    Einsele H, Steidle M, Vallbracht A, Saal JG, Ehninger G, Muller CA (1991) Early occurrence of human cytomegalovirus infection after bone marrow transplantation as demonstrated by the polymerase chain technique. Blood 77: 1104–1110Google Scholar
  24. 24.
    Elfenbein GJ, Siddiqui T, Rand KH, Graham-Pole J, Marcus RB, Mendenhall NP, Goedert TM, Wikle-Fisher T, Gross SA, Weiner RS (1990) Successful strategy for prevention of cytomegalovirus interstitial pneumonia after human leukocyte antigen-identical bone marrow transplantation. Rev Infect Dis 12 Suppl 7: S805-S810Google Scholar
  25. 25.
    Gast GC de, Gratama JW, Verdonck LF, van Heugten HG, Zwaan FE, Philips IM, Mudde GC (1989) The influence of T-cell depletion on recovery of T-cell proliferation to herpesviruses and Candida after allogeneic bone marrow transplantation. Transplantation 48: 111–115Google Scholar
  26. 26.
    Gluckman E, Lotsberg J, Devergie A, Zhao XM, Melo R, Gomez-Morales M, Nebout T, Mazeron MC, Perol Y (1983) Prophylaxis of herpes infections after bone-marrow transplantations by oral acyclovir. Lancet 2: 706–708Google Scholar
  27. 27.
    Goodrich JM, Mori M, Gleaves CA, DuMond C, Cays M, Ebeling DF, Buhles WC, DeArmond B, Meyers JD (1991) Early treatment with gancyclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation. N Engl J Med 325: 1601–1607Google Scholar
  28. 28.
    Graham-Pole J, Camitta B, Casper J, Elfenbein G, Gross S, Herzig R, Koch P, Mahoney D, Marcus R, Munoz L, et al. (1988) Intravenous immunoglobulin may lessen all forms of infection in patients receiving allogeneic bone marrow transplantation for acute lymphoblastic leukemia: a pediatric oncology group study. Bone Marrow Transplant 3: 559–566Google Scholar
  29. 29.
    Greenberg P, Goodrich J, Riddell S (1991) Adoptive immunotherapy of human cytomegalovirus infection: potential role in protection from disease progression. Transplant Proc 23: 97–101Google Scholar
  30. 30.
    Grob JP, Grundy JE, Prentice HG, Griffiths PD, Hoffbrand AV, Hughes MD, Tate T, Wimperis JZ, Brenner MK (1987) Immune donors can protect marrow-transplant recipients from severe cytomegalovirus infections. Lancet 1: 774–776Google Scholar
  31. 31.
    Kraemer KG, Neiman PE, Reeves WC, Thomas ED (1978) Prophylactic adenine arabinoside following marrow transplantation. Transplant Proc 10: 237–240Google Scholar
  32. 32.
    Kubanek B, Ernst P, Ostendorf P, Schäfer U, Wolf H (1985) Preliminary data of a controlled trial of intravenous hyperimmune globulin in the prevention of cytomegalovirus infection in bone marrow transplant recipients. Transplant Proc 17: 468–469Google Scholar
  33. 33.
    Ljungman P, Wilczek H, Gahrton G, Gustavsson A, Lundgren G, Lonnqvist B, Ringden O, Wahren B (1986) Long-term acyclovir prophylaxis in bone marrow transplant recipients and lymphocyte proliferation responses to herpes virus antigens in vitro. Bone Marrow Transplant 1: 185–192Google Scholar
  34. 34.
    Ljungman P, Niederwieser D, Pepe MS, Longton G, Storb R, Meyers JD (1990) Cytomegalovirus after marrow transplantation for aplastic aenmia. Bone Marrow Transplant 6: 295–300Google Scholar
  35. 35.
    Locasciulli A, Bacigalupo A, Van Lint MT, Chemello L, Pontisso P, Occhini D, Uderzo C, Shulman HM, Portmann B, Marmont AM, et al. (1990) Hepatitis B virus (HBV) infection and liver disease after allogeneic bone marrow transplantation: a report of 30 cases. Bone Marrow Transplant 6: 25–29Google Scholar
  36. 36.
    Locasciulli A, Bacigalupo A, Van Lint MT, Tagger A, Uderzo C, Portmann B, Shulman HM, Alberti A (1991) Hepatitis C virus infection in patients undergoing allogeneic bone marrow transplantation. Transplantation 52: 315–318Google Scholar
  37. 37.
    Mackinnon S, Burnett AK, Crawford RJ, Cameron S, Leask BG, Sommerville RG (1988) Seronegative blood products prevent primary cytomegalovirus infection after bone marrow transplantation. J Clin Pathol 41: 948–950Google Scholar
  38. 38.
    Matthews DE, Farewell VT (1988) Using and understanding medical statistics. Karger, BaselGoogle Scholar
  39. 39.
    Meyers JD, Flournoy N, Thomas ED (1980) Infection with herpes simplex and cell-mediated immunity after marrow transplant. J Infect Dis 142: 338–346Google Scholar
  40. 40.
    Meyers JD, Flournoy N, Thomas ED (1980) Cytomegalovirus infection and specific cell-mediated immunity after marrow transplant. J Infect Dis 142: 816–824Google Scholar
  41. 41.
    Meyers JD, Leszczynski J, Zaia JA, Flournoy N, Newton B, Snydman DR, Wright GG, Levin MJ, Thomas ED (1983) Prevention of cytomegalovirus infection by cytomegalovirus immune globulin after marrow transplantation. Ann Intern Med 98: 442–446Google Scholar
  42. 42.
    Meyers JD, Flournoy N, Thomas ED (1986) Risk factors for cytomegalovirus infection after human bone marrow transplantation. J Infect Dis 153: 478–488Google Scholar
  43. 43.
    Meyers JD, Flournoy N, Sanders JE, McGuffin RW, Newton BA, Fisher LD, Lum LG, Appelbaum FR, Doney K, Sullivan KM, et al. (1987) Prophylactic use of human leukocyte interferon after allogeneic marrow transplantation. Ann Intern Med 107: 809–816Google Scholar
  44. 44.
    Meyers JD, Reed EC, Shepp DH, Thornquist M, Dandliker PS, Vicary CA, Flournoy N, Kirk LE, Kersey JH, Thomas ED, et al. (1988) Acyclovir for prevention of cytomegalovirus infection and disease after allogeneic marrow transplantation. N Engl J Med 318: 70–75Google Scholar
  45. 45.
    Miller W, Flynn P, McCullough J, Balfour HHJ, Goldman A, Haake R, McGlave P, Ramsay N, Kersey J (1986) Cytomegalovirus infection after bone marrow transplantation: an association with acute graft-v-host disease. Blood 67: 1162–1167Google Scholar
  46. 46.
    Miller WJ, McCullough J, Balfour HHJ, Haake RJ, Ramsay NK, Goldman A, Bowman R, Kersey J (1991) Prevention of cytomegalovirus infection following bone marrow transplantation: a randomized trial of blood product screening. Bone Marrow Transplant 7: 227–234Google Scholar
  47. 47.
    Miyamura K, Takeyama K, Kojima S, Minami S, Matsuyama K, Morishima Y, Kodera Y (1989) Hemorrhagic cystitis associated with urinary excretion of adenovirus type 11 following allogeneic bone marrow transplantation. Bone Marrow Transplant 4: 533–535Google Scholar
  48. 48.
    O'Reilly RJ, Reich L, Gold J, Kirkpatrick D, Dinsmore R, Kapoor K, Condie R (1983) A randomized trial of intravenous hyperimmunglobulin for the prevention of cytomegalovirus (CMV) infection following marrow transplantation: preliminary results. Transplant Proc 15: 1405–1411Google Scholar
  49. 49.
    Paulin T, Ringden O, Lonnqvist B, Wahren B, Nilsson B (1986) The importance of pre-bone marrow transplantation serology in determining subsequent cytomegalovirus infection. An analysis of risk factors. Scand J Infect Dis 18: 199–209Google Scholar
  50. 50.
    Petersen FB, Bowden RA, Thornquist M, Meyers JD, Buckner CD, Counts GW, Nelson N, Newton BA, Sullivan KM, McIver J, et al. (1987) The effect of prophylactic intravenous immune globulin on the incidence of septicemia in marrow transplant recipients. Bone Marrow Transplant 2: 141–147Google Scholar
  51. 51.
    Pillay D, Webster A, Lee D, Prentice HG, Griffiths PD (1991) Cytomegalovirus excretion after bone marrow transplantation cannot be predicted from the pre-transplant level of IgG antibodies. J Med Virol 33: 257–259Google Scholar
  52. 52.
    Reusser P, Riddell S, Meyers JD, Greenberg P (1991) Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. Blood 78: 1373–1380Google Scholar
  53. 53.
    Riddel SR, Watanabe KS, Goodrich JM, Li CR, Agha ME, Greenberg PD (1991) Reconstitution of CD8+ cytomegalovirus (CMV)-specific T-cell immunity after bone marrow transplant by adoptive immunotherapy with T-cell clones. Blood 78 [Suppl]: 77a (Abstract)Google Scholar
  54. 54.
    Ringden O, Lonnqvist B, Gahrton G, Bolme P, Tollemar J, Wahren B, Lernestedt JO (1986) Comparison of two dose regimens using foscarnet for severe cytomegalovirus infections in 20 bone marrow transplant recipients. Bone Marrow Transplant [Suppl]: 41–42Google Scholar
  55. 55.
    Ringden O, Pihlstedt P, Volin L, Nikoskelainen J, Lonnqvist B, Ruutu P, Ruutu T, Toivanen A, Wahren B (1987) Failure to prevent cytomegalovirus infection by cytomegalovirus hyperimmune plasma: a randomized trial by the Nordic Bone Marrow Transplantation Group. Bone Marrow Transplant 2: 299–305Google Scholar
  56. 56.
    Saral R, Burns WH, Laskin OL, Santos GW, Leitman PS (1981) Acyclovir prophylaxis of herpes simplex virus infections. N Engl J Med 305: 63–67Google Scholar
  57. 57.
    Schlaifer D, Rubie H, Attal M, Sanguignol F, Calot JP, Puel J, Regnier C, Pris J (1990) Severe cytomegalovirus (CMV) infections after allogeneic bone marrow transplantation (BMT) and seronegative blood products: unique role of donor's immunity. 1st International Conference on the Prevention of Infection, Nice PD2 042: (Abstract)Google Scholar
  58. 58.
    Schmeiser T, Heit W, Arnold R, Bunjes D, Wiesneth M, Hertenstein B, Hampl W, Heimpel H (1987) Cytomegalovirus (CMV) infections in patients receiving CMV-IgG-hyperimmunoglobulin prophylaxis after bone-marrow transplantation. Klin Wochenschr 65: 967–974Google Scholar
  59. 59.
    Schmidt GM, Horak DA, Niland JC, Duncan SR, Forman SJ, Zaia JA (1991) A randomized, controlled trial of prophylactic gancyclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants. N Engl J Med 324: 1005–1011Google Scholar
  60. 60.
    Schuchtner LM, Wingard JR, Piantadosi S, Burns WH, Santos GW, Sarai R (1989) Herpes zoster infection after autologous bone marrow transplantation. Blood 74: 1424–1427Google Scholar
  61. 61.
    Schuler U, Vallbracht A, Einsele H, Gruber M, Mayer G, Ehninger G (1991) Incidence of positive CMV cultures during BMT in relation to CMV serology before the procedure. EBMT-Congress, Cortina D'Ampezzo: 31 (Abstract)Google Scholar
  62. 62.
    Selby PJ, Powles RL, Easton D, Perren TJ, Stolle K, Jameson B, Fiddian AP, Tryhorn Y, Stern H (1989) The prophylactic role of intravenous and long-term oral acyclovir after allogeneic bone marrow transplantation. Br J Cancer 59: 434–438Google Scholar
  63. 63.
    Shapiro RS, McClain K, Frizzera G, Gajl-Peczalska KJ, Kersey JH, Blazar BR, Arthur DC, Patton DF, Greenberg JS, Burke B, et al. (1988) Epstein-Barr virus-associated B-cell lymphoproliferative disorders following bone marrow transplantation. Blood 71: 1234–1243Google Scholar
  64. 64.
    Shepp DH, Dandliker PS, Flournoy N, Meyers JD (1987) Sequential intravenous and twice-daily oral acyclovir for extended prophylaxis of herpes simplex virus infections in marrow transplant patients. Transplantation 43: 654–658Google Scholar
  65. 65.
    Shields AF, Hackman RC, Fife KH, Corey L, Meyers JD (1985) Adenovirus infections in patients undergoing bone-marrow transplantation. N Engl J Med 312: 529–533Google Scholar
  66. 66.
    Sullivan KM, Kopecky KJ, Jocom J, Fisher L, Buckner CD, Meyers JD, Counts GW, Bowden RA, Peterson FB, Witherspoon RP, et al. (1990) Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation. N Engl J Med 323: 705–712Google Scholar
  67. 67.
    Taylor CE, Sviland L, Pearson AD, Dobb M, Reid MM, Kernahan J, Craft AW, Hamilton PJ, Proctor S (1990) Virus infections in bone marrow transplant recipients: a three-year prospective study. J Clin Pathol 43: 633–637Google Scholar
  68. 68.
    Verdonck LF, de Graan-Hentzen YC, Dekker AW, Mudde GC, de Gast GC (1987) Cytomegalovirus seronegative platelets and leukocyte-poor red blood cells from random donors can prevent primary cytomegalovirus infection after bone marrow transplantation. Bone Marrow Transplant 2: 73–78Google Scholar
  69. 69.
    Villmer E, Devergie A, Gluckman E (1986) Lymphadenopathy AIDS virus (LAV) infection after bone marrow transplantation. Bone Marrow Transplant [Suppl 1]: 37Google Scholar
  70. 70.
    Wade JC, Newton B, Flournoy N, Meyers JD (1984) Oral acyclovir for prevention of herpes simplex virus reactivation after marrow transplantation. Ann Intern Med 100: 823–828Google Scholar
  71. 71.
    Weiner RS, Horowitz MM, Gale RP, Dicke KA, van Bekkum DW, Masaoka T, Ramsay NK, Rimm AA, Rozman C, Bortin MM (1989) Risk factors for interstitial pneumonia following bone marrow transplantation for severe aplastic anaemia. Br J Haematol 71: 535–543Google Scholar
  72. 72.
    Winston DJ, Pollard RB, Ho WG, Gallagher JG, Rasmussen LE, Huang SN, Lin CH, Gossett TG, Merigan TC, Gale RP (1982) Cytomegalovirus immune plasma in bone marrow transplant recipients. Ann Intern Med 97: 11–18Google Scholar
  73. 73.
    Winston DJ, Ho WG, Lin GH, Bartoni K, Budinger MD, Gale RP, Champlin RE (1985) Use of a polyvalent intravenous immunoglobulin or specific cytomegalovirus hyperimmunoglobulin for modification of cytomegalovirus infections and prevention of interstitial pneumonias following bone marrow transplantation. Immun Infekt 13: 296–301Google Scholar
  74. 74.
    Winston DJ, Ho WG, Lin CH, Bartoni K, Budinger MD, Gale RP, Champlin RE (1987) Intravenous immune globulin for prevention of cytomegalovirus infection and interstitial pneumonia after bone marrow transplantation. Ann Intern Med 106: 12–18Google Scholar
  75. 75.
    Winston DJ, Ho WG, Champlin RE (1990) Cytomegalovirus infections after allogeneic bone marrow transplantation. Rev Infect Dis 12 [Suppl 7]: S776-S792Google Scholar
  76. 76.
    Yoshikawa T, Suga S, Asano Y, Nakashima T, Yazaki T, Sobue R, Hirano M, Fukuda M, Kojima S, Matsuyama T (1991) Human herpesvirus-6 infection in bone marrow transplantation. Blood 78: 1381–1384Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • U. Schuler
    • 1
  • G. Ehninger
    • 1
  1. 1.Abteilung Innere Medizin IIMedizinische Klinik der Universität TübingenTübingenGermany

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