Seminars in Hematology
Volume 43, Issue 1 , Pages 70-80 , January 2006

Diagnosis and Treatment of Chronic Graft-Versus-Host Disease

  • Andrew L. Gilman

      Affiliations

    • Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC.
    • Corresponding Author InformationAddress correspondence to Andrew Gilman, MD, University of North Carolina School of Medicine, 418 MacNider Hall, Chapel Hill, NC 27517.
  • ,
  • Jonathan Serody

      Affiliations

    • Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.

References 

  1. Lee SJ , Vogelsang G , Flowers ME . Chronic graft-versus-host disease . Biol Blood Marrow Transplant . 2003;9:215–233
  2. Higman MA , Vogelsang GB . Chronic graft versus host disease . Br J Haematol . 2004;125:435–454
  3. Ratanatharathorn V , Ayash L , Lazarus HM , Fu J , Uberti JP . Chronic graft-versus-host disease (clinical manifestation and therapy) . Bone Marrow Transplant . 2001;28:121–129
  4. Vogelsang GB . How I treat chronic graft-versus-host disease . Blood . 2001;97:1196–1201
  5. Stewart BL , Storer B , Storek J , Deeg HJ , Storb R , Hansen JA , et al.   Duration of immunosuppressive treatment for chronic graft-versus-host disease . Blood . 2004;104:3501–3506
  6. Nghiem P . The “drug vs graft-vs-host disease” conundrum gets tougher, but there is an answer (The challenge to dermatologists) . Arch Dermatol . 2001;137:75–76
  7. Holler E . Cytokines, viruses, and graft-versus-host disease . Curr Opin Hematol . 2002;9:479–484
  8. Jacobsohn DA , Schechter T , Seshadri R , Thormann K , Duerst R , Kletzel M . Eosinophilia correlates with the presence or development of chronic graft-versus-host disease in children . Transplantation . 2004;77:1096–1100
  9. Sullivan KM , Mori M , Sanders J , Siadak M , Witherspoon RP , Anasetti C , et al.   Late complications of allogeneic and autologous marrow transplantation . Bone Marrow Transplant . 1992;10(suppl 1):127–134
  10. Lee SJ , Klein JP , Barrett AJ , Ringden O , Antin JH , Cahn JY , et al.   Severity of chronic graft-versus-host disease (association with treatment-related mortality and relapse) . Blood . 2002;100:406–414
  11. Shulman HM , Sale GE , Lerner KG , Barker EA , Weiden PL , Sullivan K , et al.   Chronic cutaneous graft-versus-host disease in man . Am J Pathol . 1978;91:545–570
  12. Jack MK , Jack GM , Sale GE , Shulman HM , Sullivan KM . Ocular manifestations of graft-v-host disease . Arch Ophthalmol . 1983;101:1080–1084
  13. Schubert MM , Sullivan KM , Morton TH , Izutsu KT , Peterson DE , Flournoy N , et al.   Oral manifestations of chronic graft-v-host disease . Arch Intern Med . 1984;144:1591–1595
  14. Strasser SI , Shulman HM , Flowers ME , Reddy R , Margolis DA , Prumbaum M , et al.   Chronic graft-versus-host disease of the liver (Presentation as an acute hepatitis) . Hepatology . 2000;32:1265–1271
  15. McDonald GB , Sullivan KM , Schuffler MD , Shulman HM , Thomas ED . Esophageal abnormalities in chronic graft-versus-host disease in humans . Gastroenterology . 1981;80:914–921
  16. Akpek G , Chinratanalab W , Lee LA , Torbenson M , Hallick JP , Anders V , et al.   Gastrointestinal involvement in chronic graft-versus-host disease (A clinicopathologic study) . Biol Blood Marrow Transplant . 2003;9:46–51
  17. Akpek G , Valladares JL , Lee L , Margolis J , Vogelsang GB . Pancreatic insufficiency in patients with chronic graft-versus-host disease . Bone Marrow Transplant . 2001;27:163–166
  18. Schultz KR , Green GJ , Wensley D , Sargent MA , Magee JF , Spinelli JJ , et al.   Obstructive lung disease in children after allogeneic bone marrow transplantation . Blood . 1994;84:3212–3220
  19. Dudek AZ , Mahaseth H , DeFor TE , Weisdorf DJ . Bronchiolitis obliterans in chronic graft-versus-host disease (Analysis of risk factors and treatment outcomes) . Biol Blood Marrow Transplant . 2003;9:657–666
  20. Schwarer AP , Hughes JM , Trotman-Dickenson B , Krausz T , Goldman JM . A chronic pulmonary syndrome associated with graft-versus-host disease after allogeneic marrow transplantation . Transplantation . 1992;54:1002–1008
  21. Parker P, Chao NJ, Ben-Ezra J, Slatkin N, Openshaw H, Niland JC, et al  Polymyositis as a manifestation of chronic graft-versus-host disease . Medicine (Baltimore) . 1996;75:279–285
  22. Bolger GB , Sullivan KM , Spence AM , Appelbaum FR , Johnston R , Sanders JE , et al.   Myasthenia gravis after allogeneic bone marrow transplantation (Relationship to chronic graft-versus-host disease) . Neurology . 1986;36:1087–1091
  23. Seber A , Khan SP , Kersey JH . Unexplained effusions (Association with allogeneic bone marrow transplantation and acute or chronic graft-versus-host disease) . Bone Marrow Transplant . 1996;17:207–211
  24. Spiryda LB , Laufer MR , Soiffer RJ , Antin JA . Graft-versus-host disease of the vulva and/or vagina (Diagnosis and treatment) . Biol Blood Marrow Transplant . 2003;9:760–765
  25. Rackley C , Schultz KR , Goldman FD , Chan KW , Serrano A , Hulse JE , et al.   Cardiac manifestations of graft-versus-host disease . Biol Blood Marrow Transplant . 2005;11:773–780
  26. Barbara JA , Thomas AC , Smith PS , Gillis D , Ho JO , Woodroffe AJ . Membranous nephropathy with graft-versus-host disease in a bone marrow transplant recipient . Clin Nephrol . 1992;37:115–118
  27. Rouah E , Gruber R , Shearer W , Armstrong D , Hawkins EP . Graft-versus-host disease in the central nervous system. A real entity? . Am J Clin Pathol . 1988;89:543–546
  28. Greenspan A , Deeg HJ , Cottler-Fox M , Sirdofski M , Spitzer TR , Kattah J . Incapacitating peripheral neuropathy as a manifestation of chronic graft-versus-host disease . Bone Marrow Transplant . 1990;5:349–352
  29. O’Brien TA , Eastlund T , Peters C , Neglia JP , Defor T , Ramsay NK , et al.   Autoimmune haemolytic anaemia complicating haematopoietic cell transplantation in paediatric patients (High incidence and significant mortality in unrelated donor transplants for non-malignant diseases) . Br J Haematol . 2004;127:67–75
  30. Atkinson K , Farewell V , Storb R , Tsoi MS , Sullivan KM , Witherspoon RP , et al.   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 . 1982;60:714–720
  31. Quaranta S , Shulman H , Ahmed A , Shoenfeld Y , Peter J , McDonald GB , et al.   Autoantibodies in human chronic graft-versus-host disease after hematopoietic cell transplantation . Clin Immunol . 1999;91:106–116
  32. Kulkarni S , Powles R , Treleaven J , Riley U , Singhal S , Horton C , et al.   Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants . Blood . 2000;95:3683–3686
  33. Ferrara JL , Deeg HJ . Graft-versus-host disease . N Engl J Med . 1991;324:667–674
  34. Romagnani S , Parronchi P , D’Elios MM , Romagnani P , Annunziato F , Piccinni MP , et al.   An update on human Th1 and Th2 cells . Int Arch Allergy Immunol . 1997;113:153–156
  35. Hess A , Thoburn C , Chen W , Horwitz L . Autoreactive T-cell subsets in acute and chronic syngeneic graft-versus-host disease . Transplant Proc . 2001;33:1754–1756
  36. De Wit D , Van Mechelen M , Zanin C , Doutrelepont JM , Velu T , Gerard C , et al.   Preferential activation of Th2 cells in chronic graft-versus-host reaction . J Immunol . 1993;150:361–366
  37. McCormick LL , Zhang Y , Tootell E , Gilliam AC . Anti-TGF-beta treatment prevents skin and lung fibrosis in murine sclerodermatous graft-versus-host disease (A model for human scleroderma) . J Immunol . 1999;163:5693–5699
  38. Anderson BE , McNiff JM , Jain D , Blazar BR , Shlomchik WD , Shlomchik MJ . Distinct roles for donor- and host-derived antigen-presenting cells and costimulatory molecules in murine chronic graft-versus-host disease (Requirements depend on target organ) . Blood . 2005;105:2227–2234
  39. Canninga-van Dijk MR , van der Straaten HM , Fijnheer R , Sanders CJ , van den Tweel JG , Verdonck LF . Anti-CD20 monoclonal antibody treatment in 6 patients with therapy-refractory chronic graft-versus-host disease . Blood . 2004;104:2603–2606
  40. Tsoi MS , Storb R , Dobbs S , Santos E , Thomas ED . Specific suppressor cells and immune response to host antigens in long-term human allogeneic marrow recipients (Implications for the mechanisms of graft-host tolerance and chronic graft-versus-host disease) . Transplant Proc . 1981;13:237–240
  41. Clark FJ , Gregg R , Piper K , Dunnion D , Freeman L , Griffiths M , et al.   Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4+CD25high regulatory T cells . Blood . 2004;103:2410–2416
  42. Sullivan KM , Shulman HM , Storb R , Weiden PL , Witherspoon RP , McDonald GB , et al.   Chronic graft-versus-host disease in 52 patients (Adverse natural course and successful treatment with combination immunosuppression) . Blood . 1981;57:267–276
  43. Shulman HM , Sullivan KM , Weiden PL , McDonald GB , Striker GE , Sale GE , et al.   Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients . Am J Med . 1980;69:204–217
  44. Akpek G , Zahurak ML , Piantadosi S , Margolis J , Doherty J , Davidson R , et al.   Development of a prognostic model for grading chronic graft-versus-host disease . Blood . 2001;97:1219–1226
  45. Akpek G , Lee SJ , Flowers ME , Pavletic SZ , Arora M , Lee S , et al.   Performance of a new clinical grading system for chronic graft-versus-host disease (A multicenter study) . Blood . 2003;102:802–809
  46. Sullivan KM , Witherspoon RP , Storb R , Weiden P , Flournoy N , Dahlberg S , et al.   Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-v-host disease (Prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation) . Blood . 1988;72:546–554
  47. Koc S, Leisenring W, Flowers ME, Anasetti C, Deeg HJ, Nash RA, et al  Therapy for chronic graft-versus-host disease (A randomized trial comparing cyclosporine plus prednisone versus prednisone alone) . Blood . 2002;100:48–51
  48. Sullivan KM , Witherspoon RP , Storb R , Deeg HJ , Dahlberg S , Sanders JE , et al.   Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease . Blood . 1988;72:555–561
  49. Flowers ME , Lee S , Vogelsang G . An update on how to treat chronic GVHD . Blood . 2003;102:2312; (letter)
  50. Parker PM , Chao N , Nademanee A , O’Donnell MR , Schmidt GM , Snyder DS , et al.   Thalidomide as salvage therapy for chronic graft-versus-host disease . Blood . 1995;86:3604–3609
  51. Koc S , Leisenring W , Flowers ME , Anasetti C , Deeg HJ , Nash RA , et al.   Thalidomide for treatment of patients with chronic graft-versus-host disease . Blood . 2000;96:3995–3996
  52. Busca A , Saroglia EM , Lanino E , Manfredini L , Uderzo C , Nicolini B , et al.   Mycophenolate mofetil (MMF) as therapy for refractory chronic GVHD (cGVHD) in children receiving bone marrow transplantation . Bone Marrow Transplant . 2000;25:1067–1071
  53. Baudard M , Vincent A , Moreau P , Kergueris MF , Harousseau JL , Milpied N . Mycophenolate mofetil for the treatment of acute and chronic GVHD is effective and well tolerated but induces a high risk of infectious complications (A series of 21 BM or PBSC transplant patients) . Bone Marrow Transplant . 2002;30:287–295
  54. Gilman AL , Chan KW , Mogul A , Morris C , Goldman FD , Boyer M , et al.   Hydroxychloroquine for the treatment of chronic graft-versus-host disease . Biol Blood Marrow Transplant . 2000;6:327–334
  55. Johnston LJ , Brown J , Shizuru JA , Stockerl-Goldstein KE , Stuart MJ , Blume KG , et al.   Rapamycin (sirolimus) for treatment of chronic graft-versus-host disease . Biol Blood Marrow Transplant . 2005;11:47–55
  56. Raj K , Narayanan S , Augustson B , Ho A , Mehta P , Duncan N , et al.   Rituximab is effective in the management of refractory autoimmune cytopenias occurring after allogeneic stem cell transplantation . Bone Marrow Transplant . 2005;35:299–301
  57. Cutler C , Miklos D , Lee SJ , Woo SBNT , Bienfang D , Klickstein L , et al.   Rituximab therapy for steroid-refractory chronic GVHD (Safety and efficacy analysis) . Blood . 2004;104:619a
  58. Jacobsohn DA , Browning B , Thormann K , Higman M , Phelps ML , Chen AR , et al.   Pentostatin (Efficacy in refractory chronic GVHD in children) . Blood . 2004;104:619a
  59. Akpek G , Lee SM , Anders V , Vogelsang GB . A high-dose pulse steroid regimen for controlling active chronic graft-versus-host disease . Biol Blood Marrow Transplant . 2001;7:495–502
  60. Gaziev D , Lucarelli G , Polchi P , Angelucci E , Galimberti M , Giardini C , et al.   A three or more drug combination as effective therapy for moderate or severe chronic graft-versus-host disease . Bone Marrow Transplant . 2001;27:45–51
  61. Foss FM , Divenuti GM , Chin K , Sprague K , Grodman H , Klein A , et al.   Prospective study of extracorporeal photopheresis in steroid-refractory or steroid-resistant extensive chronic graft-versus-host disease (Analysis of response and survival incorporating prognostic factors) . Bone Marrow Transplant . 2005;35:1187–1193
  62. Seaton ED , Szydlo RM , Kanfer E , Apperley JF , Russell-Jones R . Influence of extracorporeal photopheresis on clinical and laboratory parameters in chronic graft-versus-host disease and analysis of predictors of response . Blood . 2003;102:1217–1223
  63. Vogelsang GB , Wolff D , Altomonte V , Farmer E , Morison WL , Corio R , et al.   Treatment of chronic graft-versus-host disease with ultraviolet irradiation and psoralen (PUVA) . Bone Marrow Transplant . 1996;17:1061–1067
  64. Arora M , Wagner JE , Davies SM , Blazar BR , Defor T , Enright H , et al.   Randomized clinical trial of thalidomide, cyclosporine, and prednisone versus cyclosporine and prednisone as initial therapy for chronic graft-versus-host disease . Biol Blood Marrow Transplant . 2001;7:265–273
  65. Carnevale-Schianca F , Martin P , Sullivan K , Flowers M , Gooley T , Anasetti C , et al.   Changing from cyclosporine to tacrolimus as salvage therapy for chronic graft-versus-host disease . Biol Blood Marrow Transplant . 2000;6:613–620
  66. Mookerjee B , Altomonte V , Vogelsang G . Salvage therapy for refractory chronic graft-versus-host disease with mycophenolate mofetil and tacrolimus . Bone Marrow Transplant . 1999;24:517–520
  67. Vogelsang GB , Farmer ER , Hess AD , Altamonte V , Beschorner WE , Jabs DA , et al.   Thalidomide for the treatment of chronic graft-versus-host disease . N Engl J Med . 1992;326:1055–1058
  68. Browne PV , Weisdorf DJ , DeFor T , Miller WJ , Davies SM , Filipovich A , et al.   Response to thalidomide therapy in refractory chronic graft-versus-host disease . Bone Marrow Transplant . 2000;26:865–869
  69. Rovelli A , Arrigo C , Nesi F , Balduzzi A , Nicolini B , Locasciulli A , et al.   The role of thalidomide in the treatment of refractory chronic graft-versus-host disease following bone marrow transplantation in children . Bone Marrow Transplant . 1998;21:577–581
  70. Lee SJ , Wegner SA , McGarigle CJ , Bierer BE , Antin JH . Treatment of chronic graft-versus-host disease with clofazimine . Blood . 1997;89:2298–2302
  71. Chiang KY , Abhyankar S , Bridges K , Godder K , Henslee-Downey JP . Recombinant human tumor necrosis factor receptor fusion protein as complementary treatment for chronic graft-versus-host disease . Transplantation . 2002;73:665–667
  72. Apisarnthanarax N , Donato M , Korbling M , Couriel D , Gajewski J , Giralt S , et al.   Extracorporeal photopheresis therapy in the management of steroid-refractory or steroid-dependent cutaneous chronic graft-versus-host disease after allogeneic stem cell transplantation (feasibility and results) . Bone Marrow Transplant . 2003;31:459–465
  73. Salvaneschi L , Perotti C , Zecca M , Bernuzzi S , Viarengo G , Giorgiani G , et al.   Extracorporeal photochemotherapy for treatment of acute and chronic GVHD in childhood . Transfusion . 2001;41:1299–1305

PII: S0037-1963(05)00173-3

doi: 10.1053/j.seminhematol.2005.09.008

Seminars in Hematology
Volume 43, Issue 1 , Pages 70-80 , January 2006