Graft-Versus-Host Disease and the Role of Blood Product Irradiation

  • S. F. Leitman
Part of the Developments in Hematology and Immunology book series (DIHI, volume 19)


Antigenic differences between the donor and the recipient in a blood transfusion may lead to a variety of immunologic reactions following transfusion. Most frequently, this involves immunologic rejection of transfused red cells, white cells, or platelets. However, on rare occasions the reaction may occur in the opposite direction, and immunologically active lymphocytes in a transfused unit may generate a severe reaction against the recipient. This is known as a graft-versus-host (GvH) reaction. It has become clear that GvH reactions may occur whenever immunologically competent allogeneic lymphocytes are transfused into an immunocompromized host.


Blood Product Acute GvHD Exchange Transfusion Severe Combine Immunodeficiency Severe Combine Immunodeficiency Disease 
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  1. 1.
    Billingham RE, Brent L. A simple method for inducing tolerance of skin homo-grafts in mice. Transplant Bull 1957;4:67–71.PubMedGoogle Scholar
  2. 2.
    Simonsen M. The impact on the developing embryo and newborn animal of adult homologous cells. Acta Pathol Microbiol Scand 1957;40:480–500.PubMedGoogle Scholar
  3. 3.
    Korngold P, Sprent J. Lethal graft-versus-host disease after bone marrow transplantation across minor histocompatibility barriers in mice. J Exp Med 1978;148:1687–98.PubMedCrossRefGoogle Scholar
  4. 4.
    Rolink AG, Gleichman E. Allosuppressor- and allohelper- T cells in acute and chronic graft-vs.-host disease. III. Different Lyt subsets induce different pathological syndromes. J Exp Med 1983;158:546–58.PubMedCrossRefGoogle Scholar
  5. 5.
    Yunis EJ, Good RA, Smith J, Stutman O. Protection of lethally irradiated mice by spleen cells from neonatally thymectomized mice. Proc Natl Acad Sci USA 1974;71:2544–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Vallera DA, Soderling CC, Carlson GJ, Kersey JH. Bone marrow transplantation across major histocompatibility barriers in mice. Effect of elimination of T cells from donor grafts by treatment with monoclonal Thy-1.2 plus complement. Transplantation 1981;31:218–22.PubMedCrossRefGoogle Scholar
  7. 7.
    Korngold R, Sprent J. Features of T cells causing H-2-restricted lethal graft-vs.-host disease across minor histocompatibility barriers. J Exp Med 1982;155: 872–83.PubMedCrossRefGoogle Scholar
  8. 8.
    Thomas ED, Storb R, Clift RA, et al. Bone marrow transplantation. N Engl J Med 1975;292:832–43.PubMedCrossRefGoogle Scholar
  9. 9.
    Storb R. Pathophysiology and prevention of graft-versus-host disease. In: McCullough J, Sandler SG (eds). Advances in immunobiology: Blood cell antigens and bone marrow transplantation. New York: Alan R. Liss 1984:337–66.Google Scholar
  10. 10.
    Deeg HJ, Storg R. Graft-versus-host disease: pathophysiological and clinical aspects. Ann Rev Med 1984;35:11–24.PubMedCrossRefGoogle Scholar
  11. 11.
    Rose WC, Rodey GE, Rimm AR, Truitt RI, Bortin M. Mitigation of graft-versus-host disease in mice by treatment of donors with bacterial endotoxin. Exp Haematol 1976;4:90–6.Google Scholar
  12. 12.
    Ramsay NKC, Kersey JH, Robinson LL, et al. A randomized study of the prevention of graft-versus-host disease. N Engl J Med 1982;306:392–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Deeg HJ, Storb R, Thomas ED, et al. Cyclosporine as prophylaxis for graft-versus-host disease: a randomized study in patients undergoing marrow transplantation for acute nonlymphoblastic leukemia. Blood 1985;65:1325–34.PubMedGoogle Scholar
  14. 14.
    Storb R, Deeg HJ, Whitehead J, et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft-versus-host disease after marrow transplantation for leukemia. N Engl J Med 1986;314:729–35.PubMedCrossRefGoogle Scholar
  15. 15.
    Prentice HG, Janossy G, Price-Jones L, et al. Depletion of T lymphocytes in donor marrow prevents significant graft-versus-host disease in matched allogeneic leukemic marrow transplant recipients. Lancet 1984;i:472–5.CrossRefGoogle Scholar
  16. 16.
    Waldmann H, Hale G, Cividalli G, et al. Elimination of graft-versus-host disease by in vitro depletion of alloreactive lymphocytes with a monoclonal rat anti-human antibody. Lancet 1984;ii:483–5.CrossRefGoogle Scholar
  17. 17.
    Mitsuyasu RT, Champlin RE, Gale RP. Treatment of donor bone marrow with monoclonal anti-T-cell antibody and complement for the prevention of graft-versus-host disease. An Intern Med 1986;105:20–6.Google Scholar
  18. 18.
    Martin PJ, Hansen JA, Buckner CD, et al. Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts. Blood 1985;66:664–72.PubMedGoogle Scholar
  19. 19.
    Filipovich AH, Vallera DA, Youle RJ, et al. Ex vivo treatment of donor bone marrow with anti-T-cell immunotoxins for prevention of graft-versus-host disease. Lancet 1984;i:469–71.CrossRefGoogle Scholar
  20. 20.
    Reisner Y, Kapoor N, Kirkpatrick D, et al. Transplantation for severe combined immunodeficiency with HLA-A,B,D, DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells. Blood 1983;61: 341–48.PubMedGoogle Scholar
  21. 21.
    Noga SJ, Donnenberg AD, Schwartz CL, Strauss LC, Civin CI, Santos GW. Development of a simplified counterflow centrifugation elutriation procedure for deletion of lymphocytes from human bone marrow. Transplantation 1986;41:220–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Betzhold J, Hong R. Fatal graft-versus-host disease after a small leukocyte transfusion in a patient with lymphoma and varicella. Pediatrics 1978;62:63–6.PubMedGoogle Scholar
  23. 23.
    Rosen PC, Huestis DW, Corrigan JJ. Acute leukemia and granulocyte transfusion: Fatal graft-versus-host reaction following transfusion of cells obtained from normal donors. J Pediatr 1978;93:268–70.PubMedCrossRefGoogle Scholar
  24. 24.
    Woods WG, Lubin BH. Fatal graft-versus-host disease following a blood transfusion in a child with neuroblastoma. Pediatrics 1981;67:217–21.PubMedGoogle Scholar
  25. 25.
    Hathaway WE, Fulginiti VA, Pierce CW, et al. Graft-versus-host reaction following a single blood transfusion. JAMA 1967;201:139–44.CrossRefGoogle Scholar
  26. 26.
    Siimes MA, Koskimies S. Chronic graft-versus-host disease after blood transfusions confirmed by incompatible HLA antigens in bone marrow. Lancet 1982; i:42–3.CrossRefGoogle Scholar
  27. 27.
    Wieden PL, Zuckerman N, Hansen JA. Fatal graft-versus-host disease in a patient with lymphoblastic leukemia following normal granulocyte transfusions. Blood 1981;57:328–32.Google Scholar
  28. 28.
    Dinsmore RE, Straus DJ, Pollack MS, et al. Fatal graft-versus-host disease following blood transfusion in Hodgkin’s disease documented by HLA typing. Blood 1980;55:831–4.PubMedGoogle Scholar
  29. 29.
    Schmidmeier W, Feil W, Gebhart W, et al. Fatal graft-versus-host reaction following granulocyte transfusion. Blut 1982;45:115–9.PubMedCrossRefGoogle Scholar
  30. 30.
    De Dobbeleer GD, Ledoux-Corbusier MH, Achten GA Graft-versus-host reaction. An ultrastructural study. Arch Dermatol 1975;111:1597–602.PubMedCrossRefGoogle Scholar
  31. 31.
    Seemayer TA, Bolande RP. Thymic involution mimicking thymic dysplasia. A consequence of transfusion-induced graft-versus-host disease in a premature infant. Arch Pathol Lab Med 1980;104:141–4.PubMedGoogle Scholar
  32. 32.
    Hathaway WE, Brangle RW, Nelson TL, Roeckel IE. Aplastic anemia and alymphocytosis in an infant with hypogammaglobulinemia: Graft-versus-host reaction? J Pediatr 1966;68:713–22.PubMedCrossRefGoogle Scholar
  33. 33.
    Bohm N, Kleine W, Enzel U. Graft-versus-host disease in two newborns after repeated blood transfusions because of rhesus incompatibility. Beitr Path Vol 1977;160:381–400.Google Scholar
  34. 34.
    Naiman JL, Punnett HH, Lischner HW, Destine ML, Arey JB. Possible graft-versus-host reaction after intrauterine transfusion for Rh erythroblastosis fetalis. N Engl J Med 1969;281:697–701.PubMedCrossRefGoogle Scholar
  35. 35.
    Parkman R, Mosier D, Umansky I, Cochran W, Carpenter CB, Rosen FS. Graft-versus-host disease after intrauterine and exchange transfusions for hemolytic disease of the newborn. N Engl J Med 1974;290:359–63.PubMedCrossRefGoogle Scholar
  36. 36.
    Martin B, Robin H, Williams R, Ornela W. Neonatal graft-versus-host disease following transfusion of maternal platelets. Transfusion 1983;23:417a.Google Scholar
  37. 37.
    Douglas SD, Fudenberg HH. Graft-versus-host reaction in Wiskott-Aldrich syndrome: Antemortem diagnosis of human GvH in an immunologic deficiency disease. Vox Sang 1969;16:172–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Rubinstein A, Radl J, Cottier H, Rossi E, Gugler E. Unusual combined immunodeficiency syndrome exhibiting kappa-IgD paraproteinemia, residual gut-immunity and graft-versus-host reaction after plasma infusion. Acta Pediatr Scand 1973;62:365–72.CrossRefGoogle Scholar
  39. 39.
    Park BH, Good RA, Gate J, Burke B. Fatal graft-versus-host reaction following transfusion of allogeneic blood and plasma in infants with combined immunodeficiency disease. Transplant Proc 1974;6:385–7.PubMedGoogle Scholar
  40. 40.
    Pollack MS, Kirkpatrick D, Kapoor N, Dupont B, O’Reilly R. Identification by HLA typing of intrauterine-derived maternal T cells in four patients with severe combined immunodeficiency. N Engl J Med 1982;307:662–6.PubMedCrossRefGoogle Scholar
  41. 41.
    Jacobs JC, Blanc WA, de Capoa A, et al. Complement deficiency and chromosomal breaks in a case of Swiss-type agammaglobulinemia. Lancet 1986;i: 499–503.Google Scholar
  42. 42.
    Hathaway WE, Githens JH, Blackburn WR, Fulginiti V, Kempe CH. Aplastic anemia, histiocytosis and erythrodermia in immunologically deficient children. N Engl J Med 1965;273:953–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Niethammer D, Goldmann SF, Flad HD, et al. Graft-versus-host reaction after blood transfusion in a patient with cellular immunodeficiency: The role of histocompatibility testing. Eur J Pediatr 1979;132:43–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Gatti RA, Platt N, Pomerance HH, et al. Hereditary lymphopenic agammaglobulinemia associated with a distinctive form of short-limbed dwarfism and ectodermal dysplasia. J Pediatr 1969;75:675–84.PubMedCrossRefGoogle Scholar
  45. 45.
    Robertson WR, Berry CL, Macaulay JC, Soothill JF. Partial immunodeficiency and graft-versus-host disease. Arch Dis Child 1971;46:571–4.CrossRefGoogle Scholar
  46. 46.
    Fauci AS, Macher AM, Longo DL, et al. Acquired immunodeficiency syndrome: Epidemiologic, clinical, immunologic, and therapeutic considerations. Ann Intern Med 1984;100:92–106.PubMedGoogle Scholar
  47. 47.
    Cohen D, Weinstein H, Mihm M, Yankee R. Nonfatal graft-versus-host disease occurring after transfusion with leukocytes and platelets obtained from normal donors. Blood 1979;53:1053–7.PubMedGoogle Scholar
  48. 48.
    Schmitz N, Kayser W, Gassmann W, et al. Two cases of graft-versus-host disease following transfusion of nonirradiated blood products. Blut 1982;44:83–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Ford JM, Cullen MH, Lucey JJ, Tobias JS, Lister TA. Fatal graft-versus-host disease following transfusion of granulocytes from normal donors. Lancet 1976; ii:1167–9.CrossRefGoogle Scholar
  50. 50.
    Lowenthal RM, Menon C, Challis DR. Graft-versus-host disease in consecutive patients with acute myeloid leukemia treated with blood cells from normal donors. Aust NZ J Med 1981;11:179–83.CrossRefGoogle Scholar
  51. 51.
    Groff P, Torhorst J, Speck B, et al. Die Graft-versus-Host Krankheit, eine wenig bekannte Komplikation der Bluttransfusion. Schweiz Med Wschr 1976;106:634–9.PubMedGoogle Scholar
  52. 52.
    Von Fliedner V, Higby DJ, Kim U. Graft-versus-host reaction following blood transfusion. Am J Med 1982;72:951–61.CrossRefGoogle Scholar
  53. 53.
    Schiffer CA, Aisner J, Dutcher JA, Wiernik PH. Sustained post-transfusion granulocyte increments following transfusion of leukocytes obtained from donors with chronic myelogenous leukemia. Am J Hematol 1983;15:65–74.PubMedCrossRefGoogle Scholar
  54. 54.
    Yeager AM, Kaizer H, Santos GW, et al. Autologous bone marrow transplantation in patients with acute nonlymphocytic leukemia, using ex vivo marrow treatment with 4-hydroperoxycyclophosphamide. N Engl J Med 1986;315:141–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Crowley JP, Skrabut EM, Valeri CR. Immunocompetent lymphocytes in previously frozen washed red cells. Vox Sang 1974;26:513–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Sprent J, Anderson RE, Miller JF. Radiosensitivity of T and B lymphocytes. II. Effect of irradiation on response of T cells to alloantigens. Eur J Immunol 1974;4:204–10.PubMedCrossRefGoogle Scholar
  57. 57.
    Hall EJ. Radiobiology for the radiologist. Hagerstown: Harper & Row 1978.Google Scholar
  58. 58.
    Valerius NH, Johansen KS, Nielsen OS, Platz P, Rosenkvist J, Sorensen H. Effect of in vitro x-irradiation on lymphocyte and granulocyte function. Scand J Hematol 1981;27:9–18.CrossRefGoogle Scholar
  59. 59.
    Button LN, de Wolf WC, Newburger PE, Jacobson MS, Kevy SV. The effects of irradiation on blood components. Transfusion 1981;21:419–26.PubMedCrossRefGoogle Scholar
  60. 60.
    Coifman RE, Good RA, Meuwissen HJ. The function of irradiated blood elements. I. Limitations on the response to phytohemagglutinin as an indicator of immunocompetence in irradiated lymphocytes. Proc Soc Exp Biol Med 1971; 137:155–60.PubMedGoogle Scholar
  61. 61.
    Moore GL, Ledford ME. Effects of 4000 rad irradiation on the in vitro storage properties of packed red cells. Transfusion 1985;25:583–5.PubMedCrossRefGoogle Scholar
  62. 62.
    Greenberg ML, Chanana AD, Cronkite EP, Schiffer LM, Stryckmans PA. Extracorporeal irradiation of blood in man, radiation resistance of circulating platelets. Radiat Res 1968;35:147–54.PubMedCrossRefGoogle Scholar
  63. 63.
    Moroff G, George VM, Siegl AM, Luban NLC. The influence of irradiation on stored platelets. Transfusion 1986;26:453–6.PubMedCrossRefGoogle Scholar
  64. 64.
    Kodis C, Read EJ, Leitman SF, Carter CS, Klein HG. Effect of pre-storage irradiation on posttransfusion platelet survival. Transfusion 1986;26:568a.Google Scholar
  65. 65.
    Holley TR, van Epps DE, Harvey RL. Effect of high doses of radiation on human neutrophil Chemotaxis, phagocytosis, and morphology. Am J Pathol 1974;75:61–8.PubMedGoogle Scholar
  66. 66.
    Patrone F, Dallegri F, Brema F, Sacchetti C. Effects of irradiation and storage on granulocytes harvested by continuous-flow centrifugation. Exp Hematol 1979;7:131–6.PubMedGoogle Scholar
  67. 67.
    Buescher ES, Holland PV, Gallin JL Radiation-induced defective oxygen metabolism in leukocytes prepared for transfusion as assessed by nitroblue tetazolium reduction. Clin Res 1983;31:309a.Google Scholar
  68. 68.
    Atomic Energy of Canada Limited. Gammacell 1000—Blood Irradiator. Kanata, Ontario 1984;1–4.Google Scholar
  69. 69.
    Kahn RA, Duffy BF, Rodey GG. Ultraviolet irradiation of platelet concentrates abrogates lymphocyte activation without affecting platelet function in vitro. Transfusion 1985;25:547–50.PubMedCrossRefGoogle Scholar

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© Martinus Nijhoff Publishing, Boston 1987

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  • S. F. Leitman

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