The Role of the Microflora in Graft-versus-Host Disease After Allogeneic Bone Marrow Transplantation

  • D. W. van Bekkum
  • P. J. Heidt
Part of the Argenteuil Symposia book series (ARGENTEUIL)


Currently, allogeneic bone marrow transplantation (BMT) is an accepted treatment for many fatal diseases of the haemopoietic system, among them severe aplastic anaemia [1] and leukaemia [2]. Furthermore, patients suffering from fatal hereditary diseases that are associated with a dysfunction of the lymphoid system, such as severe combined immunodeficiency [3], and patients with inherited severe metabolic disorders [4] are being treated with bone marrow grafts. In total about 2500 patients are transplanted annually world-wide in 160 BMT centres.


Bone Marrow Transplantation Acute GvHD Allogeneic Bone Marrow Allogeneic Bone Marrow Transplantation Donor Bone Marrow 
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  1. 1.
    Löwenberg B, Gale RP (1985) Aplastic anaemia. In: van Bekkum DW, Löwenberg B (eds) Bone marrow transplantation, biological mechanism and clinical practice. Marcel Dekker, New York, pp 409–433Google Scholar
  2. 2.
    Dicke KA, Zander AR, Vellekoop L, Spitzer G, Verma DS (1985) The treatment of leukemia. In: van Bekkum DW, Löwenberg B (eds) Bone marrow transplantation, biological mechanisms and clinical practice. Marcel Dekker, New York, pp 435–474Google Scholar
  3. 3.
    Dooren LJ, Vossen JM (1985) Severe combined immunodeficiency: Reconstitution of the immune system following bone marrow transplantation. In: van Bekkum DW, Löwenberg B (eds) Bone marrow transplantation, biological mechanisms and clinical practice. Marcel Dekker, New York, pp 351–381Google Scholar
  4. 4.
    Barranger JA (1984) Marrow transplantation in genetic disease. N Engl J Med 311: 1629–1631PubMedCrossRefGoogle Scholar
  5. 5.
    Gale RP, Bortin MM, van Bekkum DW, Biggs JC, Dicke KA, Gluckman E, Good RA, Hoffmann RG, Kay HEM, Kersey JH, Marmont A, Masaoka T, Rimm A, van Rood JJ, Zwaan FE (1987) Risk factors for acute graft-versus-host disease. Br J Haematol 67: 397–406PubMedCrossRefGoogle Scholar
  6. 6.
    Uphoff DE, Law LW (1958) Genetic factors influencing irradiation protection by bone marrow. II. The histocompatibility-2 (H-2) locus. J Natl Cancer Inst 20: 617–624PubMedGoogle Scholar
  7. 7.
    van Bekkum DW (1964) The selective elimination of immunologically competent cells from bone marrow and lymphatic cell mixtures. I. Effect of storage at 4°C. Transplantation 2: 393–404CrossRefGoogle Scholar
  8. 8.
    van Bekkum DW (1972) Use and abuse of hemopoietic cell grafts in immune deficiency diseases. Transpl Rev 9: 3–53Google Scholar
  9. 9.
    van Bekkum DW, de Vries MJ (1967) Radiation chimeras. Academic Press, New YorkGoogle Scholar
  10. 10.
    van Bekkum DW, Roodenburg J, Heidt PJ, van der Waaij D (1974) Mitigation of secondary disease of allogeneic mouse radiation chimeras by modification of the intestinal microflora. J Natl Cancer Inst 52: 401–404PubMedGoogle Scholar
  11. 11.
    Jones JM, Wilson R, Bealmear PM (1971) Mortality and gross pathology of secondary disease in germfree mouse radiation chimeras. Radiat Res 45: 577–580PubMedCrossRefGoogle Scholar
  12. 12.
    Truitt RL (1978) Application of germfree techniques to the treatment of leukemia in AKR mice by allogeneic bone marrow transplantation. In: Waters H (ed) Immunotherapy. Garland STPM Press, New York, pp 431–452 (The handbook of cancer immunology, vol 5 )Google Scholar
  13. 13.
    Heit H, Wilson R, Fliedner TM, Kohne E (1973) Mortality of secondary disease in antibiotic treated mouse radiation chimeras. In: Heneghan JB (ed) Germfree research: biological effects of gnotobiotic environment. Academic Press, New York, pp 477–483Google Scholar
  14. 14.
    van Bekkum DW (1977) Bone marrow transplantation. Transpl Proc 9: 147–154Google Scholar
  15. 15.
    van Bekkum DW, Knaan S (1977) Role of bacterial flora in development of intestinal lesions from graft versus host reaction. J Natl Cancer Inst 58: 787–790PubMedGoogle Scholar
  16. 16.
    Wagemaker G (1986) Problems and prospects of histoincompatible bone marrow transplantation studied in rhesus monkeys. In: Hagenbeek A, Lowenberg B (eds) Minimal residual disease in acute leukemia. Martinus Nijhoff, Dordrecht, pp 363–373CrossRefGoogle Scholar
  17. 17.
    Heidt PJ, Wagemaker G, Knaan-Shanzer S, van Bekkum DW (1981) Two distinct types of late onset graft-versus-host disease after bone marrow transplantation in lethally irradiated mice. Transplantation 32: 263–264PubMedCrossRefGoogle Scholar
  18. 18.
    Heidt PJ (1989) Gnotobiotics and bone marrow transplantation: experimental and clinical studies. Thesis, University of LeidenGoogle Scholar
  19. 19.
    Broerse JJ, van Bekkum DW, Hollander CF, Davids JAG (1978) Mortality of monkeys after exposure to fission neutrons and the effect of autologous bone marrow transplantation. Int J Radiat Biol 34: 253–264CrossRefGoogle Scholar
  20. 20.
    Dicke KA, van Bekkum DW (1971) Allogeneic bone marrow transplantation after elimination of immunocompetent cells by means of density gradient centrifugation. Transpl Proc 3: 666–668Google Scholar
  21. 21.
    Heidt PJ, Vriesendorp HM, Zurcher C, de Groot CW, Klapwijk WM (1981) Selective gastrointestinal decontamination in dogs undergoing allogeneic bone marrow transplantation. In: Sasaki S, Ozawa A, Hashimoto K (eds) Recent advances in germfree research. Tokai University Press, Tokyo, pp 579–582Google Scholar
  22. 22.
    Storb R, Prentice RL, Buckner CD, Clift RA, Appelbaum F, Deeg J, Doney K, Hansen JA, Mason M, Sanders JE, Singer J, Sullivan KM, Witherspoon RP, Thomas ED (1983) Graft- versus-host disease and survival in patients with aplastic anemia treated by marrow grafts from HLA-identical siblings. N Engl J Med 308: 302–307PubMedCrossRefGoogle Scholar
  23. 23.
    Mahmoud HK, Schaefer UW, Schuning F, Schmidt CG, Bamberg M, Haralambie E, Linzenmeier G, Hantschke D, Grosse-Wilde H, Luboldt W, Richter HJ (1984) Laminar air flow versus barrier nursing in marrow transplant recipients. Blut 49: 375–381PubMedCrossRefGoogle Scholar
  24. 24.
    Schmeiser T, Kurrle E, Arnold R, Heit W, Krieger D, Kubanek B, Heimpel H (1984) Application of antimicrobial prophylactic treatment to the prevention of infection and graft- versus-host disease in allogeneic bone marrow transplantation (BMT). Exp Haematol 12 (suppl 15): 105–106Google Scholar
  25. 25.
    Storb R, Thomas ED (1985) Graft-versus-host disease in dog and man: the Seattle experience. Immunol Rev 88: 215–238PubMedCrossRefGoogle Scholar
  26. 26.
    Leblond V, Belanger C, Dreyfus F, Brunet F, Gabarre J, Asselain B, Binet L (1987) Interest of laminar air flow for prevention of GvHD and infections in BMT for leukaemia and lymphoma. Bone Marrow Transpl 2 (suppl 1): 181Google Scholar
  27. 27.
    Skinhøj P, Jacobsen N, Høiby N, Faber V and the Copenhagen Bone Marrow Transplant Group (1987) Strict protective isolation in allogeneic bone marrow transplantation; effect on infectious complications, fever and graft versus host disease. Scand J Infect Dis 19: 91 – 96PubMedCrossRefGoogle Scholar
  28. 28.
    Vossen JM, Heidt PJ (1988) Effect of gnotobiotic measures on infection and graft-versus-host disease in children treated with bone marrow transplantation for leukemia or severe aplastic anaemia. In: Gnotobiology and its applications. Proceedings of the IXth International Symposium on Gnotobiology. Fondation Marcel Mérieux, Lyon Cedex, pp 140–143Google Scholar
  29. 29.
    van der Waaij D, Vossen JM, Korthals-Altes C (1973) Patient isolators designed in the Netherlands. In: Heneghan JB (ed) Germfree research. Biological effect of gnotobiotic environment. Academic Press, New York, pp 31 - 36Google Scholar
  30. 30.
    Thomas ED, Storb R, Clift RA, Fever A, Johnson LF, Neiman PE, Leraer KG, Glucksberg H, Buckner CD (1975) Bone marrow transplantation. N Engl J Med 292: 895–902PubMedCrossRefGoogle Scholar
  31. 31.
    van der Waaij D, Andreas AH (1971) Prevention of airborne contamination and cross- contamination in germ-free mice by laminar flow. J Hyg, Camb 69: 83–89CrossRefGoogle Scholar
  32. 32.
    Foo MC, Lee A (1974) Antigenic cross-reaction between mouse intestine and a member of the autochthonous microflora. Infect Immunol 9: 1066–1069Google Scholar

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© Springer-Verlag London Limited 1990

Authors and Affiliations

  • D. W. van Bekkum
  • P. J. Heidt

There are no affiliations available

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