Chronic graft-versus-host disease: Pathogenesis and clinical management

Drugs

Volumn 66, Issue 8, 2006, Pages 1041-1057

  Pérez Simón, José A ^a   Sánchez Abarca, Ignacio ^a   Díez Campelo, María ^a   Caballero, Dolores ^a   San Miguel, Jesús ^a  

^a HOSPITAL UNIVERSITARIO DE SALAMANCA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ALEMTUZUMAB; ALLOANTIGEN; ANTIFUNGAL AGENT; ANTIINFECTIVE AGENT; ARTIFICIAL TEAR; AUTOANTIGEN; BASILIXIMAB; BECLOMETASONE; BETAMETHASONE; BETAMETHASONE DIPROPIONATE; BORTEZOMIB; CALCINEURIN INHIBITOR; CLOBETASOL; CORTICOSTEROID; CYCLOSPORIN A; CYTOKINE ANTIBODY; DACLIZUMAB; ETANERCEPT; HYDROCORTISONE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IMMUNOSUPPRESSIVE AGENT; METHOTREXATE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PENTOSTATIN; PREDNISONE; RAPAMYCIN; RITUXIMAB; TACROLIMUS; THALIDOMIDE; URSODEOXYCHOLIC ACID;

ABDOMINAL CRAMP; ALLOGENEIC STEM CELL TRANSPLANTATION; ANTIBODY PRODUCTION; ANTIGEN PRESENTING CELL; B LYMPHOCYTE ACTIVATION; CELL DAMAGE; CELL PROLIFERATION; CELL SURVIVAL; CHRONIC GRAFT VERSUS HOST DISEASE; CLINICAL FEATURE; CLINICAL TRIAL; CYTOLYSIS; CYTOPENIA; CYTOTOXIC T LYMPHOCYTE; DENDRITIC CELL; DISEASE CLASSIFICATION; DISEASE SEVERITY; DOSE RESPONSE; DRUG BINDING; DRUG FORMULATION; DRUG INHIBITION; DRUG MEGADOSE; HEMOLYTIC UREMIC SYNDROME; HIGH RISK PATIENT; HLA SYSTEM; HLA TYPING; HUMAN; HYPERCHOLESTEROLEMIA; HYPERTRIGLYCERIDEMIA; IMMUNE RESPONSE; IMMUNOSUPPRESSIVE TREATMENT; INCIDENCE; INFECTION COMPLICATION; KARNOFSKY PERFORMANCE STATUS; KIDNEY FAILURE; MESENCHYMAL STEM CELL; NEUROTOXICITY; NEUTROPENIA; NONHUMAN; OINTMENT; OPPORTUNISTIC INFECTION; PATHOGENESIS; PROGNOSIS; PUVA; QUALITY OF LIFE; RECURRENCE RISK; REGULATORY T LYMPHOCYTE; REMISSION; REVIEW; RISK ASSESSMENT; SALVAGE THERAPY; SURVIVAL TIME; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TARGET ORGAN; TREATMENT FAILURE; TREATMENT INDICATION; TREATMENT OUTCOME; TREATMENT PLANNING; TREATMENT RESPONSE;

ANIMALS; CHRONIC DISEASE; DENDRITIC CELLS; GRAFT VS HOST DISEASE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; PHOTOPHERESIS; RISK FACTORS; STEM CELL TRANSPLANTATION; TISSUE THERAPY;

EID: 33745360878     PISSN: 00126667     EISSN: 00126667     Source Type: Journal    
DOI: 10.2165/00003495-200666080-00002     Document Type: Review

References (146)

1. Przepiorka D, Smith TL, Folloder J, et al. Risk factors for acute graft-versus-host disease after allogenic blood stem cell transplantation. Blood 1999; 94: 1465-70
2. Blaise D, Kuentz M, Fortanier C, et al. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Société Française de Greffe de Moelle. J Clin Oncol 2000; 18 (3): 537-46
3. Bensinger WI, Martin PJ, Storer B, et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 2001; 344 (3): 175-81
4. Mohty M, Kuentz M, Michallet M, et al. cGVHD after allogeneic blood stem cell transplantation: long-term results of a randomized study. Blood 2002; 100 (9): 3128-34
5. Powels R, Metha J, Kulkarni S, et al. Allogenic blood and bone marrow stem cell transplantation in haematological malignant diseases: a randomised trial. Lancet 2000; 355 (9211): 1231-7
6. Flowers ME, Parker PM, Johnston LJ, et al. Comparison of cronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial. Blood 2002; 100 (2): 415-9
7. Díez-Campelo M, Pérez-Simón JA, González- Porras JR, et al. Quality of life assessment in patients undergoing reduced intensity conditioning allogeneic vs autologous transplantation: results of a prospective study. Bone Marrow Transplant 2004; 34 (8): 729-38
8. Ferrara JL, Cooke KR, Teshima T. The pathophysiology of acute graft versus host disease. Int J Hematol 2003; 78: 181-7
9. Hill GR, Ferrara JL. The primacy of the gastrointestinal tract as a target organ of acute graft versus host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation. Blood 2000; 95: 2754-9
10. Reddy P. Pathophysiology of acute graft versus host disease. Hematol Oncol 2003; 21: 149-61
11. Goker H, Haznedaroglu I, Chao N. Acute graft versus host disease: pathobiology and management. Exp Hematol 2001; 29: 259-77
12. Couriel D, Caldera H, Champlin R, et al. Acute graft versus host disease: pathophysiology, clinical manifestations and management. Cancer 2004; 101: 1936-46
13. Hakim F, Mackall C. The immune system: effector and target of graft versus host disease. In: Ferrara J, Deeg J, Burakoff S, editors. Graft versus host disease. New York: Marcel Dekker Inc., 1997: 275-290
14. Lee S. New approaches for preventing and treating chronic graft versus host disease. Blood 2005; 105: 4200-6
15. Shulman HM, Sullivan KM, Weiden PL, et al. Chronic graft versus host disease syndrome in man: a long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204-17
16. Atkinson K, Horowitz MM, Gale RP, et al. Consensus among bone marrow transplanters for diagnosis, grading and treatment of chronic graft versus host disease. Bone Marrow Transplant 1989; 4: 247-54
17. Akpek G, Zahurak M, Piantadosi S, et al. Development of a prognostic model for grading chronic graft versus host disease. Blood 2001; 97: 1219-26
18. Martino R, Caballero D, Perez-Simon JA, et al. Evidence for a graft-versus-leukemia effect after allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning in acute myelogenous leukemia and myelodysplastic syndroms. Blood 2002; 100 (6): 2243-5
19. Pérez-Simón JA, Martino R, Alegre A, et al. Chronic but not acute graft versus host disease improves outcome in multiple myeloma patients after nonmyeloablative allogeneic transplantation. Br J Haematol 2003; 121: 104-8
20. Pérez-Simón J, Díez-Campelo M, Martino R, et al. Impact of CD34+ cell dose on the outcome of patients undergoing reduced intensity conditioning allogeneic peripheral blood stem cell transplantation. Blood 2003; 102 (3): 1108-13
21. Pérez-Simón JA, Caballero D, Lopez-Pérez R, et al. Chimerism and minimal residual disease monitoring after reduced intensity conditioning (RIC) allogeneic transplantation. Leukemia 2002; 16 (8): 1423-31
22. Gratwohl A, Brand R, Apperley J, et al. Graft-versus-host disease and outcome in HLA-identical sibling transplantations for chronic myeloid leukaemia. Blood 2002; 100: 3877-86
23. Weiden PL, Flournoy N, Thomas ED, et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med 1979; 300: 1068-73
24. Weiden PL, Sullivan KM, Flournoy N, et al. Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 1981; 304: 1529-33
25. Sullivan KM, Weiden PL, Storb R, et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood 1989; 73: 1720-8
26. Ringden O, Hermans J, Labopin M, et al. A. The highest leukaemia-free survival after allogeneic bone marrow transplantation is seen in patients with grade I acute graft-versus-host disease. Acute and Chronic Leukaemia Working Parties of the European Group for Blood and Marrow Transplantation (EBMT). Leuk Lymphoma 1996; 24: 71-9
27. Atkinson K, Incefy GS, Storb R, et al. Low serum thymic hormone levels in patients with chronic graft versus host disease. Blood 1982; 59: 1073-7
28. Vogelsang G. How I treat chronic graft versus host disease. Blood 2001; 97: 1196-201
29. Sullivan K. Graft versus host disease. In: Blume K, Forman S, Appelbaum F, editors. Thoma's hematopoietic cell transplantation. Malden (MA): Blackwell Science Inc., 2004; 50: 635-64
30. Morris SC, Cheek RL, Cohen PL, et al. Allotype-specific immunoregulation of autoantibody production by host B cells in chronic graft versus host disease. J Immunol 1990; 144: 916-22
31. Saitoh T, Fujiwara M, Asakura H. L3T4+ T cells induce hepatic lesions resembling primary biliary cirrhosis in mice with graft versus host reaction due to major histocompatibility complex class II disparity. Clin Immunol Immunopathol 1991; 59: 449-61
32. Kier P, Penner E, Bakos S, et al. Autoantibodies in chronic GVHD: high prevalence of antinucleolar antibodies. Bone Marrow Transplant 1990; 6: 93-6
33. Wesierska-Gadek J, Penner E, Hitchman E, et al. Nucleolar proteins B23 and C23 as target antigens in chronic graft versus host disease. Blood 1992; 79: 1081-6
34. Garsili CG, Pennline KJ, Smith SR, et al. Cytokine gene expression in mice undergoing chronic graft versus host disease. Mol Immunol 1993; 30: 669-77
35. h2 cells in chronic graft versus host reaction. J Immunol 1993; 150: 361-6
36. Jordan W, Brookes P, Szydlo R, et al. IL-13 production by donor T cells is prognostic of acute graft versus host disease following unrelated donor stem cell transplantation. Blood 2004; 103: 717-24
37. h2 cytokine production during the early course of acute and chronic murine graft-versus-host disease. Regulatory role of donor CD8+ T cells. J Immunol 1995; 155 (5): 2396-406
38. Sanchez-Guijo FM, Sánchez-Abarca LI, Bueno C, et al. Long-term immune recovery of patients undergoing allogeneic stem cell transplantation: a comparison with their respective sibling donors. Biol Blood Marrow Transplant 2005; 11 (5): 354-61
39. Korholz D, Kunst D, Hempel L, et al. Decreased IL 10 and increased interferon gamma production in patients with chronic graft versus host disease after allogeneic bone marrow transplantation. Bone Marrow Transplant 1997; 19: 691-5
40. Steinman RM, Nussenzweig MC. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc Natl Acad Sci U S A 2002; 99: 351-8
41. Matzinger P. The danger model: a renewed sense of self. Science 2002; 296: 301-5
42. Shlomchik WC, Couzens MS, Tang CB, et al. Prevention of graft versus host disease by inactivation of host antigen presenting cells. Science 1999; 285: 412-5
43. Anderson B, McNiff J, Jain D, et al. Distinct roles for donor and host derived antigen presenting cells and costimulaory molecules in murine chronic graft versus host disease: requirements depend on target organ. Blood 2005; 105: 2227-34
44. Zorn E, Kim HT, Lee SJ, et al. Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease. Blood 2005; 106 (8): 2903-11
45. Clark F, Gregg R, Piper K, et al. Chronic graft versus host disease is associated with increased numbers of peripheral blood CD4+CD25 high regulatory T cells. Blood 2004; 103: 2410-6
46. Sullivan K, Agura E, Anasetti C. Chronic graft versus host disease in other late complications of bone marrow transplantation. Semin Hematol 1991; 28: 250-9
47. Flomenberg N, Baxter-Lowe LA, Confer D, et al. Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome. Blood 2004; 104: 1923-30
48. Petersdorf EW, Anasetti C, Martín PJ, et al. Limits of HLA mismatching in unrelated hematpoietic cell transplantation. Blood 2003; 9: 610-5
49. Hurley CK, Baxter LA, Logan B, et al. National marrow donor program HLA-matching guidelines for unrelated marrow transplants. Biol Blood Marrow Transplant 1999; 5: 347-56
50. Kollman C, Howe C, Anasetti C, et al. Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood 2001; 98: 2043-51
51. Santo Tomás LH, Loberiza FR, Klein JP, et al. Risk factors for bronchiolitis obliterans in allogeneic hematopoietic stem-cell transplantation for leukemia. Chest 2005; 128 (1): 153-61
52. Miklos DB, Kim HT, Guo L, et al. Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission. Blood 2005; 105 (7): 2973-8
53. Blaise D, Kuentz M, Fortanier C, et al. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Société Française de Greffe de Moelle. J Clin Oncol 2000; 18 (3): 537-46
54. Bensinger WI, Martin PJ, Storer B, et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 2001; 344 (3): 175-81
55. Mohty M, Kuentz M, Michallet M, et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation: long-term results of a randomized study. Blood 2002; 100 (9): 3128-34
56. Powels R, Metha J, Kulkarni S, et al. Allogenic blood and bone marrow stem cell transplantation in haematological malignant diseases: a randomised trial. Lancet 2000; 355 (9211): 1231-7
57. Cutler C, Giri S, Jeyapalan S, et al. Acute and chronic graft versus host disease after allogeneic peripheral blood stem cell transplantation: a metaanalysis. J Clin Oncol 2001; 19: 3685-91
58. Schmitz N, Beksac M, Hasenclever D, et al. Transplantation of mobilized peripheral blood cells to HLA-identical siblings with standard-risk leukaemia. Blood 2002; 100: 761-7
59. Couban S, Simpson D, Barnett M, et al. A randomized multicenter comparison of bone marrow and peripheral blood in recipients of matched sibling allogeneic transplants for myeloid malignancies. Blood 2002; 100: 1525-31
60. Flowers ME, Parker PM, Johnston LJ, et al. Comparison of chronic graft-versus-host disease after transplantation of peripheral blood stem cells versus bone marrow in allogeneic recipients: long-term follow-up of a randomized trial. Blood 2002; 100 (2): 415-9
61. Laughlin MJ, Eapen M, Rubinstein P, et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004; 351: 2265-75
62. Vanderson R, Lobopin M, Sanz G, et al. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukaemia. N Engl J Med 2004; 351: 2276-85
63. Bacigalupo A, Lamparelli T, Bruzzi P, et al. Antithymovyte globulin for graft versus host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from GITMO. Blood 2001; 98: 2942-7
64. + selected cells from peripheral blood. Blood 1997; 89: 3967-73
65. Pérez-Simón JA, Kottaridis P, Martino R, et al. Non-myeloablative transplants with or without CAMPATH-1H: comparison between two prospective studies in patients with lymphoproliferative disorders. Blood 2002; 100 (9): 3121-7
66. Pavletic S, Carter S, Kernan N, et al. Influence of T cell depletion on chronic graft versus host disease: results of a multicenter randomised trial in unrelated donor transplantation. Blood 2005; 106 (9): 3308-13
67. Zaucha JM, Gooley T, Bensinger WI, et al. CD 34 cell dose in granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell grafts affects engrafment kinetics and development of extensive cronic graft-versus-host disease after human leucocyte antigen-identical sibling transplantation. Blood 2001; 98 (12): 3221-7
68. + dose impact donor engraftment following nonmyeloablative allogeneic stem cell transplantation in patients with solid tumors. Blood 2004; 103: 1560-3
69. Chen B, Cui X, Sempowski G, et al. Hematopoietic stem cell dose correlates with the speed of immune reconstitution after stem cell transplantation. Blood 2004; 103: 4344-52
70. Baron F, Marin MB, Storer BE, et al. High doses of transplanted CD34+ cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation. Leukemia 2005; 19 (5): 822-88
71. Bittencourt H, Rocha V, Chevret S. Association of CD 34 cell dose with hematopoietic recovery, infections, and other outcomes after HLA-identical sibling bone marrow transplantation. Blood 2002; 99 (8): 2726-33
72. Dominietto A, Lamparelli T, Raiola AM, et al. Transplant-related mortality and long-term graft function are significantly influenced by cell dose in patients undergoing allogenic marrow transplantation. Blood 2002; 100 (12): 3930-94
73. Ferrara JL, Levy R, Chao NJ. Pathophysiologic mechanisms of acute grant versus host disease. Biol Blood Marrow Transplant 1999; 5: 347-56
74. Mielcarek M, Martin PJ, Leisenring W, et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 2003; 102: 756-62
75. Pérez-Simón JA, Díez-Campelo M, Martino R, et al. Influence of the intensity of the conditioning regimen on the characteristics of acute and chronic graft versus host disease after allogeneic transplantation. Br J Haematol 2005; 130 (3): 394-403
76. Couriel DR, Saliba RM, Giralt S, et al. Acute and chronic graft-versus-host disease after ablative and nonmyeloablative conditioning for allogeneic hematopoietic transplantation. Biol Blood Marrow Transplant 2004; 10: 178-85
77. Ochs LA, Miller WJ, Filipovich AH, et al. Predictive factors for chronic graft versus host disease after histocompatible sibling donor bone marrow transplantation. Bone Marrow Transplant 1994; 13: 455-60
78. Lee S, Klein J, Barret J, et al. Severity of chronic graft versus host disease: association with treatment related mortality and relapse. Blood 2002; 100: 406-14
79. Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945-55
80. Pavletic S, Smith L, Bishop M, et al. Prognostic factors of chronic graft versus host disease after allogeneic blood stem cell transplantation. Am J Hematol 2005; 78: 265-74
81. Akpek G, Lee SL, Flowers ME, et al. Performance of a new clinical grading system for chronic graft-versus-host disease: a multicenter study. Blood 2003; 102: 802-9
82. Stewart B, Storer B, Storek J, et al. Duration of immunosuppressive treatment for chronic graft versus host disease. Blood 2004; 104: 3501-6
83. Shulman HM, Kleiner D, Lee SJ, et al. National Institutes of Health Consensus Development Project on criteria for clinical trials in chronic graft-versus-host disease: II. Pathology working group report. Biol Blood Marrow Transplant 2006; 12: 31-47
84. Syrjala KL, Chapko MK, Vitaliano PP, et al. Recovery alter allogeneic marrow transplantation: prospective study of predictors of long-term physical and psychosocial functioning. Bone Marrow Transplant 1993; 11: 319-27
85. Zittoun R, Suciu S, Watson M, et al. Quality of life in patients with acute myelogenous leucemia in prolonged first complete remission alter bone marrow transplantation (allogeneic or autologous) or chemotherapy: a cross-sectional study of EORTC-GIMEMA AML 84 trial. Bone Marrow Transplant 1997; 20: 307-15
86. Andrykowski MA, Henslee PJ, Farral MG. Physical and psychosocial functioning of adult survivors of allogeneic bone marrow transplantation. Bone Marrow Transplant 1989; 4: 75-81
87. Belec RH. Quality of life: perceptions of long-term survivors of bone marrow transplantation. Oncol Nurs Forum 1992; 19: 31-7
88. Jenkins PL, Linington A, Whittaker JA. A retrospective study of psychosocial morbidity in bone marrow transplantation recipients. Psychosomatics 1991; 32: 65-71
89. Radich J, Gehly G, Lee A, et al. Detection of bcr-abl transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia after marrow transplantation. Blood 1997; 89: 2602-9
90. Radich J, Gehly G, Gooley T, et al. Polymerase chain reaction detection of the bcr-abl fusion transcript after allogeneic marrow transplantation for chronic myeloid leukemia: results and implications in 346 patients. Blood 1995; 85: 2632-8
91. Sullivan KM, Witherspoon RP, Storb R, et al. Prednisone and azathioprine compared with prednisone and placebo for the treatment of chronic graft versus host disease: prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation. Blood 1988; 72: 546-54
92. Sullivan KM, Shulman HM, Storb R, et al. Chronic graft versus host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood 1988; 57: 267-76
93. Koc S, Leisenring W, Flowers M, et al. Therapy for chronic graft versus host disease: a randomised trial comparing cyclosporine and prednisone versus prednisone alone. Blood 2002; 100: 48-51
94. Arora M, Wagner JE, Davies SM, et al. Randomized clinical trial of thalidomide, cyclosporine and prednisone as initial therapy for chronic graft versus host disease. Biol Blood Marrow Transplant 2001; 7: 265-73
95. Koc S, Leisenring W, Flowers M, et al. Thalidomide for the treatment of patients with chronic graft versus host disease. Blood 2000; 96: 3995-6
96. Lopez F, Parker P, Nademanee A, et al. Efficacy of mycophenolate mofetil in the treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant 2005; 11: 307-13
97. Baudard M, Vincent A, Moreau P, et al. 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; 5: 287-95
98. Srinivasan R, Chakrabarti S, Walsh T, et al. Improved survival in steroid-refractory acute graft versus host disease after non-myeloablative allogeneic transplantation using a daclizumab-based strategy with comprehensive infection prophylaxis. Br J Haematol 2004; 124: 777-86
99. Przepiorka D, Kernan NA, Ippoliti C, et al. Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood 2000; 95: 83-9
100. Blaise D, Olive D, Michallet M, et al. Impairment of leukaemia-free survival by addition of interleukin-2-receptor antibody to standard graft versus-host prophylaxis. Lancet 1995; 345: 1144-6
101. Couriel DR, Saliba R, Escalon P, et al. Sirolimus in combination with tacrolimus and corticosteroids for the treatment of resistant chronic graft versus host disease. Br J Haematol 2005; 130: 409-17
102. Johnston L, Brown J, Shizuru J, et al. Rapamycin (sirolimus) for the treatment of chronic graft versus host disease. Biol Blood Marrow Transplant 2005; 11: 47-55
103. Goldberg J, Jacobson D, Margolis J, et al. Pentostatin for the treatment of chronic graft-versus-host disease in children. J Pediatr Hematol Oncol 2003; 25 (7): 584-8
104. Seaton ED, Szydlo RM, Kanfer E, et al. Influence of extracorporeal photopheresis on clinical and laboratory parameters in chronic graft-versus-host disease and analysis of predictors of response. Blood 2003; 102: 1217-23
105. Couriel D, Hosing C, Saliva R, et al. Extracorporeal photopheresis for acute and chronic graft versus host disease: does it work? Biol Blood Marrow Transplant 2006; 12: 37-40
106. Child FJ, Ratnavel R, Watkins P, et al. Extracorporeal photopheresis (ECP) in the treatment of chronic graft-versus-host disease (GVHD). Bone Marrow Transplant 1999; 23: 881-7
107. Besnier DP, Chabannes D, Mahe B, et al. Treatment of graft-versus-host disease by extracorporeal photochemotherapy: a pilot study. Transplantation 1997; 64: 49-54
108. Rossetti F, Zulian F, Dall'Amico R, et al. Extracorporeal photochemotherapy as single therapy for extensive, cutaneous, chronic graft-versus-host disease. Transplantation 1995; 59: 149-51
109. Alcindor T, Gorgun G, Miller BK. Immunomodulatory effects of extracorporeal photochemotherapy in patients with extensive chronic graft-versus-host disease. Blood 2001; 98: 1622-5
110. Ratanatharathorn V, Carson E, Reynolds C, et al. Anti-CD20 chimeric monoclonal antibody treatment of refractory immune-mediated thrombocytopenia in a patient with chronic graft-versus-host disease. Ann Intern Med 2000; 133: 275-9
111. Ratanetharathorn V, Ayash L, Reynolds C, et al. Treatment of chronic graft-versus-host disease with anti-CD20 chimeric monoclonal antibody. Biol Blood Marrow Transplant 2003; 9: 505-11
112. Canninga-Van Dijk MR, Van Der Straaten HM, Fijnheer R, et al. Anti-CD20 monoclonal antibody treatment in 6 patients with therapy refractory chronic graft-versus-host disease. Blood 2004; 104: 2603-6
113. Chiang KY, Abhyankar S, Bridges K, et al. Recombinant human tumor necrosis factor receptor fusion protein as complementary treatment for chronic graft-versus-host disease. Transplantation 2002; 73: 665-7
114. Ruutu T, Eriksson B, Remes K, et al. Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic stem cell transplantation. Blood 2002; 100: 1977-83
115. Fried RH, Murakami CS, Fisher LD, et al. Ursodeoxycholic acid treatment of refractory chronic graft-versus-host disease of the liver. Ann Intern Med 1992; 116: 624-9
116. Chiba T, Yokosuka O, Kanda T, et al. Hepatic graft-versus-host disease resembling acute hepatitis: additional treatment with ursodeoxycholic acid. Liver 2002; 22: 514-7
117. Iyer R, Hahn T, Roy H, et al. Long-term use of oral beclomethasone dipropionate for the treatment of gastrointestinal graft-versus-host disease. Biol Blood Marrow Transplant 2005; 11: 587-92
118. Margolis J, Vogelsang G. An old drug for a new disease: pentostatin (Nipent) in acute graft-versus-host disease. Semin Oncol 2000; 27: 72-7
119. Bolaños-Meade J, Jacobson D, Margolis J, et al. Pentostatin in steroid-refractory acute graft-versus-host disease. J Clin Oncol 2005; 23: 2661-8
120. Rubegni P, Cuccia A, Sbano P, et al. Role of extracorporeal photochemotherapy in patients with refractory chronic graft-versus-host disease. Br J Haematol 2005; 130: 271-5
121. Wada H, Mori A, Okada M, et al. Treatment of intestinal graft versus host disease using betamethasone enemas. Transplantation 2001; 72: 1451-3
122. Choi CJ, Nghiem P. Tacrolimus ointment in the treatment of chronic cutaneous graft-vs-host disease: a case series of 18 patients. Arch Dermatol 2001; 137 (9): 1202-6
123. Eckard A, Starke O, Stadler M, et al. Severe oral chronic graft-versus-host disease following allogeneic bone marrow transplantation: highly effective treatment with topical tacrolimus. Oral Oncol 2004; 40 (8): 811-4
124. Rizzo JD, Wingard JR, Tichelli A, et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, the Center for International Blood and Marrow Transplant Research, and the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2006; 12: 138-51
125. Solomon S, Mielke S, Savani B, et al. Selective depletion of alloreactive donor lymphocytes: a novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation. Blood 2005; 106: 1123-9
126. Martin P, Pei J, Gooley T, et al. Evaluation of a CD25 specific immunotoxin for prevention of graft versus host disease after unrelated marrow transplantation. Biol Blood Marrow Transplant 2004; 10: 552-60
127. h1 cytokines. Blood 2005 Nov 10, [Epub ahead of print]
128. Hideshima T, Richardson P, Chauhan D, et al. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis and overcomes drug resistance in human multiple myeloma cells. Cancer Res 2001; 61: 3071-6
129. Sakaguchi S. Naturally arising CD4 regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 2004; 22: 531-62
130. Suciu-Foca N, Manavalan JS, Cortesini R. Generation and function of antigen-specific supresor and regulatory T cells. Trans-pl Immunol 2003; 11: 235-44
131. Jonuleit H, Adema G, Schmitt E. Immune regulation by regulatory T cells: implications for transplantation. Transpl Immunol 2003; 11: 267-76
132. Taylor P, Lees C, Blazar B. The infusion of ex vivo activated and expanded CD4+CD25+ immune regulatory cells inhibits graft versus host disease lethality. Blood 2002; 99 (10): 3493-9
133. Godfrey W, Ge Y, Spoden D, et al. In vitro expanded human CD4+CD25+ T regulatory cells can markedly inhibit allogeneic dendritic cell stimulated MLR cultures. Blood 2004; 104 (2): 453-61
134. Battaglia M, Stabilini A, Roncarolo M. Rapamycin selectively expands CD4+CD25+FOXP3+ regulatory T cells. Blood 2005; 105 (12): 4743-8
135. Mahnke K, Qian Y, Knop J, et al. Induction of CD4+CD25+ regulatory T cells by targeting of antigens to immature dendritic cells. Blood 2003; 101 (12): 4862-9
136. Steinman R, Hawiger D, Nussenzweig M. Tolerogenic dendritic cells. Annu Rev Immunol 2003; 21: 685-711
137. Fresnay E, Garnache-Ottou F, Plumasm J, et al. Can tolerogenic dendritic cells help to modulate allo-immune responses in the setting of hematopoietic cell transplantation? Transpl Immunol 2003; 11: 259-66
138. Penna G, Adorini L. 1,25-Dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 2000; 164: 2405-11
139. Hackstein H, Taner T, Zahorchak AF, et al. Rapamycin inhibits Il-4 induced dendritic cell maturation in vitro and dendritic cell mobilization and function in vivo. Blood 2003; 101: 4457-63
140. Abe M, Thomson AW. Influence of immunosuppressive drugs on dendritis cells. Transpl Immunol 2003; 11: 357-65
141. Beith S, Borovsky Z, Mevorach D, et al. Human mesechymal stem cells alter antigen-presenting maturation and induce T-cell unresponsiveness. Blood 2005; 105: 2214-9
142. Jiang X-X, Zhang Y, Liu B, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 2005; 105: 4120-6
143. Rasmusson I, Ringdén O, Sundberg B, et al. Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms. Exp Cell Res 2005; 305: 33-41
144. Aggarwal S, Pittenger M. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105 (4): 1815-22
145. Maccario R, Podesta M, Moretta A, et al. Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype. Haematologica 2005; 90: 516-25
146. Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft versus host disease with third party haploidentical mesenchymal stem cells. Lancet 2004; 363: 1439-41