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Chronic Graft-versus-Host Disease: Pathogenesis, Diagnosis, Treatment, and Prognostic Factors

  • Conference paper
Recent Advances and Future Directions in Bone Marrow Transplantation

Part of the book series: Experimental Hematology Today—1987 ((HEMATOLOGY,volume 1987))

Abstract

Chronic graft-versus-host disease (GVHD) and associated infections are major determinants of late morbidity and mortality in 25–50% of long-term survivors of allogeneic marrow transplantation [1]. With improving supportive care during transplant, broadening criteria for donor selection and expanding indications and numbers of centers for transplant, an increasing number of long-term survivors are reported [2–4]. For primary care hematologists and oncologists, recognizing and treating late complications is of increasing importance. The following reviews the pathogenesis, diagnosis, treatment and prognosis of chronic GVHD.

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References

  1. Sullivan KM, Deeg HJ, Sanders JE, Shulman HM, Witherspoon RP, Doney K, Appelbaum FR, Schubert MM, Stewart P, Springmeyer S, McDonald GB, Storb R, Thomas ED (1984) Late complications after marrow transplantation. Semin Hematol 21:53–63

    PubMed  CAS  Google Scholar 

  2. Thomas ED (1983) Marrow transplantation for malignant diseases (Karnofsky Memorial Lecture). J Clin Oncol 1:517–531

    PubMed  CAS  Google Scholar 

  3. Beatty PG, Clift RA, Mickelson EM, Nisperos B, Flournoy N, Martin PJ, Sanders JE, Storb R, Thomas ED, Hansen JA (1985) Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med 313:765–771

    Article  PubMed  CAS  Google Scholar 

  4. Bortin MM, Rimm AA (1986) Increasing utilization of bone marrow transplantation. Transplantation 42:229–234

    Article  PubMed  CAS  Google Scholar 

  5. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, Hackman R, Tsoi M-S, Storb R, Thomas ED (1980) Chronic graft-versus-host syndrome in man: A long-term clinicopathological study of 20 Seattle patients. Am J Med 69:204–217

    Article  PubMed  CAS  Google Scholar 

  6. Sullivan KM (1986) Acute and chronic graft-versus-host disease in man. Int J Cell Cloning 4(Suppl 1):42–93

    Article  PubMed  Google Scholar 

  7. Sullivan KM, Shulman HM, Storb R, Weiden PL, Witherspoon RP, McDonald GB, Schubert MM, Atkinson K, Thomas ED (1981) Chronic graft-versus-host disease in 52 patients: Adverse natural course and successful treatment with combination immunosuppression. Blood 57:267–276

    PubMed  CAS  Google Scholar 

  8. Sullivan KM, Witherspoon R, Deeg HJ, Doney K, Appelbaum F, Sanders J, Lum L, Loughran T, Hill R, Anasetti C, Shields A, Nims J, Shulman H, Storb R, Thomas ED (1987) Chronic graft-versus-host disease in man. In: Gale RP, Champlin R, eds. Progress in bone marrow transplantation. New York: AR Liss, 473–487

    Google Scholar 

  9. Storb R, Prentice RL, Sullivan KM, Shulman HM, Deeg HJ, Doney KC, Buckner CD, Clift RA, Witherspoon RP, Appelbaum FA, Sanders JE, Stewart PS, Thomas ED (1983) Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA-identical siblings. Ann Intern Med 98:461–466

    PubMed  CAS  Google Scholar 

  10. Ringden O, Paulin T, Lonnqvist B, Nilsson B (1985) An analysis of factors predisposing to chronic graft-versus-host disease. Exp Hematol 13:1062–1067

    PubMed  CAS  Google Scholar 

  11. Lonnqvist B, Ringden O, Wahren B, Gahrton G, Lundgren G (1984) Cytomegalovirus infection associated with and preceding chronic graft-versus-host disease. Transplantation 38: 465–468

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  13. Sullivan KM, Deeg HJ, Sanders J, Klosterman A, Amos D, Shulman H, Sale G, Martin P, Witherspoon R, Appelbaum FR, Doney K, Stewart P, Meyers J, McDonald GB, Weiden P, Fefer A, Buckner CD, Storb R, Thomas ED (1986) Hyperacute GVHD in patients not given immunosuppression after allogeneic marrow transplantation. Blood 67: 1172–1175

    PubMed  CAS  Google Scholar 

  14. Storb R, Deeg HJ, Whitehead J, Appelbaum F, Beatty P, Bensinger W, Buckner CD, Clift R, Doney K, Farewell V, Hansen J, Hill R, Lum L, Martin P, McGuffin R, Sanders J, Stewart P, Sullivan K, Witherspoon R, Yee G, Thomas ED (1986) Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med 314:729–735

    Article  PubMed  CAS  Google Scholar 

  15. Seddik M, Seemayer TA, Lapp WS (1980) T cell functional defect associated with thymic epithelial cell injury induced by a graft-versus-host reaction. Transplantation 29:61–66

    Article  PubMed  CAS  Google Scholar 

  16. Tsoi M-S (1982) Immunologic mechanisms of graft-versus-host disease in man. Transplantation 33:459–464

    Article  PubMed  CAS  Google Scholar 

  17. Atkinson K, Incefy GS, Storb R, Sullivan KM, Iwata T, Dardenne M, Ochs HD, Good RA, Thomas ED (1982) Low serum thymic hormone levels in patients with chronic graft-versus-host disease. Blood 59:1073–1077

    PubMed  CAS  Google Scholar 

  18. Tutschka PJ (1987) Mechanisms of chronic GVHD. In: Gale RP, Champlin R, eds. Progress in bone marrow transplantation. New York: AR Liss, 457–472

    Google Scholar 

  19. Gleichmann E, Pals ST, Rolink AG, Radaszkiewicz T, Gleichmann H (1984) Graft-versus-host reactions: Clues to the etiopathology of a spectrum of immunological diseases. Immunol Today 5:324–332

    Article  Google Scholar 

  20. Beschorner WE, Tutschka PJ, Santos GW (1983) Chronic graft-versus-host disease in the rat radiation chimera. III. Immunology and immunopathology in rapidly induced models. Transplantation 35:224–230

    Article  PubMed  CAS  Google Scholar 

  21. Parkman R (1986) Clonal analysis of murine graft-versus-host disease. I. Phenotypic and functional analysis of T lymphocyte clones. J Immunol 136:3543–3548

    PubMed  CAS  Google Scholar 

  22. Parkman R, DeClerck Y, Champagne J, Walker S (1987) Chronic graft-versus-host disease is an autoimmune disease. In: Gale RP, Champlin R, eds. Progress in bone marrow transplantation. New York: AR Liss, 497–504

    Google Scholar 

  23. Shulman HM, Sale GE, Lerner KG, Barker EA, Weiden PL, Sullivan K, Gallucci B, Thomas ED, Storb R (1978) Chronic cutaneous graft-versus-host disease in man. Am J Pathol 91:545–570

    PubMed  CAS  Google Scholar 

  24. McDonald GB, Shulman HM, Sullivan KM, Spencer GD (1986) Intestinal and hepatic complications of human bone marrow transplantation. Gastroenterology 90:460–477,

    PubMed  CAS  Google Scholar 

  25. McDonald GB, Shulman HM, Sullivan KM, Spencer GD (1986) Intestinal and hepatic complications of human bone marrow transplantation. Gastroenterology 90:770–784

    PubMed  CAS  Google Scholar 

  26. Epstein O, Thomas HC, Sherlock S (1980) Primary biliary cirrhosis is a dry gland syndrome with features of chronic graft-versus-host disease. Lancet 1:1166–1168

    Article  PubMed  CAS  Google Scholar 

  27. Sale GE, Shulman HM, Schubert MM, Sullivan KM, Kopecky KJ, Hackman RC, Morton TH, Storb R, Thomas ED (1981) Oral and ophthalmic pathology of graft versus host disease in man: Predictive value of the lip biopsy. Hum Pathol 12:1022–1030

    Article  PubMed  CAS  Google Scholar 

  28. Burke CM, Theodore J, Dawkins KD, Yousem SA, Blank N, Billingham ME, Van Kessel A, Jamieson SW, Oyer PE, Baldwin JC, Stinson EB, Shumway NE, Robin ED (1984) Post-transplant obliterative bronchiolitis and other late lung sequelae in human heart-lung transplantation. Chest 86:824–829

    Article  PubMed  CAS  Google Scholar 

  29. Gluckman E, Janin-Mercier A (1987) Is chronic graft-versus-host disease similar to autoimmune diseases. In: Gale RP, Champlin R, eds. Progress in bone marrow transplantation. New York: AR Liss, 489–495

    Google Scholar 

  30. Schubert MM, Sullivan KM, Morton TH, Izutsu KT, Peterson DE, Flournoy N, Truelove EL, Sale GE, Buckner CD, Storb R, Thomas ED (1984) Oral manifestations of chronic graft-versus-host disease. Arch Intern Med 144:1591–1595

    Article  PubMed  CAS  Google Scholar 

  31. Jack MK, Jack GM, Sale GE, Shulman HM, Sullivan KM (1983) Ocular manifestations of graft-v-host disease. Arch Ophthalmol 101:1080–1084

    PubMed  CAS  Google Scholar 

  32. McDonald GB, Sullivan KM, Schuffler MD, Shulman HM, Thomas ED (1981) Esophageal abnormalities in chronic graft-versus-host disease in humans. Gastroenterology 80:914–921

    PubMed  CAS  Google Scholar 

  33. Corson SL, Sullivan K, Batzer F, August C, Storb R, Thomas ED (1982) Gynecologic manifestations of chronic graft-versus-host disease. Obstet Gynecol 60:488–492

    PubMed  CAS  Google Scholar 

  34. Bolger GB, Sullivan KM, Spence AM, Appelbaum FR, Johnston R, Sanders JE, Deeg HJ, Witherspoon RP, Doney KC, Nims J, Thomas ED, Storb R (1986) Myasthenia gravis after allogeneic bone marrow transplantation: Relationship to chronic graft-versus-host disease. Neurology 36:1087–1091

    PubMed  CAS  Google Scholar 

  35. Sullivan KM, Witherspoon RP, Storb R, Wei den P, Flournoy N, Dahlberg S, Deeg HJ, Sanders JE, Doney KC, Appelbaum FR, McGuffin R, McDonald G, Meyers J, Schubert MM, Gauvreau J, Shulman HM, Sale GE, Anasetti C, Loughran T, Strom S, Nims J, Thomas ED. Prednisone and azathioprine compared to prednisone and placebo for treatment of chronic graft-versus-host disease: Prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation. (submitted for publication)

    Google Scholar 

  36. Ralph DD, Springmeyer SC, Sullivan KM, Hackman RC, Storb R, Thomas ED (1984) Rapidly progressive air-flow obstruction in marrow transplant recipients: Possible association between obliterative bronchiolitis and chronic graft-versushost disease. Am Rev Respir Dis 129:641–644

    PubMed  CAS  Google Scholar 

  37. Witherspoon RP, Buckner CD, Sullivan KM, Fisher L, Clark J, Storb R, Thomas ED. Causes of late failure in patients transplanted for acute leukemia. Bone Marrow Transplantation, (in press)

    Google Scholar 

  38. Clark JG, Schwartz DA, Flournoy N, Sullivan KM, Crawford SW, Thomas ED. Risk factors for development of airflow obstruction in marrow transplant recipients. Ann Intern Med, (in press)

    Google Scholar 

  39. Lapp WS, Ghayur T, Mendes M, Seddik M, Seemayer TA (1985) The functional and histological basis for graft-versus-host-induced immunosuppression. Immunol Rev 88:107–133

    Article  PubMed  CAS  Google Scholar 

  40. Witherspoon RP (1986) Suppression and recovery of immunologic function after bone marrow transplantation. J Natl Cancer Inst 76:1321–1324

    PubMed  CAS  Google Scholar 

  41. Lum LG (1987) A review: The kinetics of immune reconstitution after human marrow transplantation. Blood 69:369–380

    PubMed  CAS  Google Scholar 

  42. Atkinson K, Farewell V, Storb R, Tsoi M-S, Sullivan KM, Witherspoon RP, Fefer A, Clift R, Goodell B, Thomas ED (1982) Analysis of late infections after human bone marrow transplantation: Role of genotypic nonidentity between marrow donor and recipient and of nonspecific suppressor cells in patients with chronic graft-versus-host disease. Blood 60:714–720

    PubMed  CAS  Google Scholar 

  43. Atkinson K, Storb R, Ochs HD, Goehle S, Sullivan KM, Witherspoon RP, Lum LG, Tsoi M-S, Sanders JE, Parr M, Stewart P, Thomas ED (1982) Thymus transplantation after allogeneic bone marrow graft to prevent chronic graft-versus-host disease in humans. Transplantation 33:168–173

    Article  PubMed  CAS  Google Scholar 

  44. Witherspoon RP, Navari R, Storb R, Sullivan KM, Doney K, Beatty P, Lum LG, Thomas ED (1987) Treatment of marrow graft recipients with thymopentin. Bone Marrow Transplantation 1:365–371

    PubMed  CAS  Google Scholar 

  45. Witherspoon RP, Hersman J, Storb R, Ochs H, Goldstein AL, McClure J, Noel D, Weiden PL, Thomas ED (1983) Thymosin fraction 5 does not accelerate reconstitution of immunologic reactivity after human marrow grafting. Br J Haematol 55: 595–608

    Article  PubMed  CAS  Google Scholar 

  46. Lum LG, Seigneuret MC, Shiobara S, Noges J, Munn N, Shough N, Jin N-R, Beatty P, Martin P, Sullivan K, Storb R, Thomas ED. Adoptively transferred immunity persists in human marrow graft recipients. In: Truitt RL, Gale RP, Bortin MM, eds. Cellular immunotherapy of cancer. New York: AR Liss, (in press)

    Google Scholar 

  47. Sullivan KM, Meyers JD, Flournoy N, Storb R, Thomas ED (1986) Early and late interstitial pneumonia following human bone marrow transplantation. Int J Cell Cloning 4(Suppl 1): 107–121

    Article  PubMed  Google Scholar 

  48. Witherspoon RP, Storb R, Ochs HD, Flournoy N, Kopecky KJ, Sullivan KM, Deeg HJ, Sosa R, Noel DR, Atkinson K, Thomas ED (1981) Recovery of antibody production in human allogeneic marrow graft recipients: Influence of time post transplantation, the presence or absence of chronic graft-versus-host disease, and antithymocyte globulin treatment. Blood 58:360–368

    PubMed  CAS  Google Scholar 

  49. Korsmeyer SJ, Elfenbein GJ, Goldman CK, Marshall SL, Waldmann TA (1982) B cell, helper T cell and suppressor T cell abnormalities contribute to disordered immunoglobulin synthesis in patients following bone marrow transplantation. Transplantation 33:184–190

    Article  PubMed  CAS  Google Scholar 

  50. Sullivan KM. Immunoglobulin therapy in bone marrow transplantation. Am J Med, (in press)

    Google Scholar 

  51. Petersen FB, Bowden RA, Thornquist M, Meyers JD, Buckner CD, Counts GW, Nelson N, Newton BA, Sullivan KM, McIver J, Thomas ED. The effect of prophylactic intravenous immune globulin on the incidence of septicemia in marrow transplant recipients. Bone Marrow Transplantation, (in press)

    Google Scholar 

  52. Sullivan KM, Storb R, Flournoy N, Weiden P, Shulman H, Deeg HJ, Witherspoon R, Thomas ED (1982) Preliminary analysis of a randomized trial of immunosuppressive therapy of chronic graft-versus-host disease (GVHD). Blood 60 (Supp 1):173a, (abstr)

    Google Scholar 

  53. Sullivan KM, Deeg HJ, Storb R, Nims J, Witherspoon R, Doney K, Appelbaum F, Thomas ED (1986) Alternating-day cyclosporine and prednisone improve survival in patients with high-risk chronic graft-versus-host disease. Exp Hematol 14:529, (abstr)

    Google Scholar 

  54. Sullivan KM, Witherspoon RP, Storb R, Deeg HJ, Dahlberg S, Sanders JE, Appelbaum FR, Doney KC, Weiden P, Anasetti C, Loughran T, Hill R, Shields TP, Shulman H, Nims J, Strom S, Thomas ED. Alternating day cyclosporine and prednisone for treatment of high-risk chronic graft-versus-host disease, (submitted for publication)

    Google Scholar 

  55. Summerfield GP, Bellingham AJ, Bunch C, Woodrow JC (1983) Successful treatment of chronic cutaneous graft-versus-host disease (GVHD) with penicillamine. Clin Lab Haemat 5:313–318

    CAS  Google Scholar 

  56. Bunjes D, Heit W, Arnold R, Schmeiser T, Heimpel H (1986) Cyclosporine as an alternative to cyclophosphamide in the treatment of chronic graft-versus-host disease. Transplantation 41:170–172

    Article  PubMed  CAS  Google Scholar 

  57. Vogelsang GB, Taylor S, Gordon G, Hess AD (1986) Thalidomide, a potent agent for the treatment of graft-versus-host disease. Transplant Proc 18:904–906

    CAS  Google Scholar 

  58. First LR, Smith BR, Lipton J, Nathan DG, Parkman R, Rappaport JM (1985) Isolated thrombocytopenia after allogeneic bone marrow transplant and chronic thrombocytopenic syndromes. Blood 65:368–374

    PubMed  CAS  Google Scholar 

  59. Anasetti C, Sullivan K, Deeg J, Slichter S (1986) Graft-versus-host disease (GVHD) is associated with autoimmune-1ike thrombocytopenia. J Cell Biochem Suppl 10D:222, (abstr)

    Google Scholar 

  60. Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED, the Seattle Marrow Transplant Team (1981) Antileukemic effect of chronic graft-versus-host disease: Contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 304:1529–1533

    Article  PubMed  CAS  Google Scholar 

  61. Sullivan KM, Fefer A, Witherspoon R, Storb R, Buckner CD, Weiden P, Schoch G, Thomas ED. Graft-versus-leukemia in man: Relationship of acute and chronic graft-versus-host disease to relapse of acute leukemia following allogeneic bone marrow transplantation. In: Truitt RL, Gale RP, Bortin MM, eds. Cellular immunotherapy of cancer. New York: AR Liss, (in press)

    Google Scholar 

  62. Greenberg PD, Cheever MA, Fefer A (1981) Eradication of disseminated murine leukemia by chemo-immunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt 1+ 2- T lymphocytes. J Exp Med 154:952–963

    Article  PubMed  CAS  Google Scholar 

  63. Mitsuyasu RT, Champlin RE, Gale RP, Ho WG, Lenarsky C, Winston D, Selch M, Elashoff R, Giorgi JV, Wells J, Terasaki P, Billing R, Feig S (1986) Treatment of donor bone marrow with monoclonal anti-T-cell antibody and complement for the prevention of graft-versus-host disease: A prospective, randomized, double-blind trial. Ann Intern Med 105:20–26

    PubMed  CAS  Google Scholar 

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Authors
  1. Keith Sullivan
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  2. Robert Witherspoon
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Editor information

Editors and Affiliations

  1. Department of Physiology, Uniformed Services University of the Health Sciences, School of Medicine, Bethesda, Maryland, 20817, USA

    Siegmund J. Baum Ph.D.

  2. Department of Oncology, The John Hopkins Hospital, Baltimore, Maryland, 21205, USA

    George W. Santos M.D. (Professor of Oncology and Medicine) (Professor of Oncology and Medicine)

  3. Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan

    Fumimaro Takaku M.D. (Professor) (Professor)

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Sullivan, K. et al. (1988). Chronic Graft-versus-Host Disease: Pathogenesis, Diagnosis, Treatment, and Prognostic Factors. In: Baum, S.J., Santos, G.W., Takaku, F. (eds) Recent Advances and Future Directions in Bone Marrow Transplantation. Experimental Hematology Today—1987, vol 1987. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-3762-4_25

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