Concise review: Acute graft-versus-host disease: Immunobiology, prevention, and treatment

Stem Cells Translational Medicine

Volumn 2, Issue 1, 2013, Pages 25-32

  Sung, Anthony D ^a   Chao, Nelson J ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Adult hematopoietic stem cells; Adult human bone marrow; Cellular therapy; Hematologic malignancies; Hematopoietic stem cell transplantation; Immune reconstitution; Peripheral blood stem cells; Transplantation tolerance

Indexed keywords

ALEMTUZUMAB; BECLOMETASONE; CIPROFLOXACIN; CYCLOPHOSPHAMIDE; CYCLOSPORIN; DENILEUKIN DIFTITOX; ETANERCEPT; IMMUNOGLOBULIN; INFLIXIMAB; MARAVIROC; METHOTREXATE; METHYLPREDNISOLONE; METRONIDAZOLE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PALIFERMIN; PENTOSTATIN; RAPAMYCIN; TACROLIMUS;

ACUTE GRAFT VERSUS HOST DISEASE; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; APOPTOSIS; BONE NECROSIS; CATARACT; CELL DIFFERENTIATION; CELL EXPANSION; CELL MIGRATION; CELL PROLIFERATION; CYTOKINE PRODUCTION; CYTOTOXICITY; DISEASE SEVERITY; HUMAN; HYPERGLYCEMIA; IMMUNE DEFICIENCY; IMMUNOBIOLOGY; INFECTION; MAJOR HISTOCOMPATIBILITY COMPLEX; MYOPATHY; OSTEOPOROSIS; PHASE 2 CLINICAL TRIAL (TOPIC); POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME; PROPHYLAXIS; PSYCHOSIS; PUVA; RANDOMIZED CONTROLLED TRIAL (TOPIC); REGULATORY T LYMPHOCYTE; REVIEW; STAGING; T LYMPHOCYTE ACTIVATION; THROMBOTIC THROMBOCYTOPENIC PURPURA; ACUTE DISEASE; ANIMAL; GRAFT VERSUS HOST REACTION; IMMUNOLOGY; IMMUNOSUPPRESSIVE TREATMENT; METABOLISM; PATHOLOGY; SEVERITY OF ILLNESS INDEX;

ACUTE DISEASE; ANIMALS; GRAFT VS HOST DISEASE; HUMANS; IMMUNOSUPPRESSION; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SEVERITY OF ILLNESS INDEX;

MLCS; MLOWN;

EID: 84873423706     PISSN: 21576564     EISSN: 21576580     Source Type: Journal    
DOI: 10.5966/sctm.2012-0115     Document Type: Review

References (97)

1. Jagasia M, Arora M, Flowers ME et al. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood 2012; 119:296-307.
2. Pasquini MC, Wang Z. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR Summary Slides, 2011. Available at http://www.cibmtr.org. Accessed 2011.
3. Kline J SS, Lazarus HM, van Besien K. Autologous graft-versus-host disease: Harnessing anti-tumor immunity through impaired selftolerance. Bone Marrow Transplant 2008;41: 505-513.
4. Dwyre DM, Holland PV. Transfusion-associated graft-versus-host disease. Vox Sang 2008;95:85-93.
5. Welniak LA, Blazar BR, Murphy WJ. Immunobiology of allogeneic hematopoietic stem cell transplantation. Annu Rev Immunol 2007; 25:139-170.
6. Zeiser R, Penack O, Holler E et al. Danger signals activating innate immunity in graft-versushost disease. J Mol Med (Berl) 2011;89:833-845.
7. Hill GR Crawford JM, Cooke KR et al. Total body irradiation and acute graft-versus-host disease: The role of gastrointestinal damage and inflammatory cytokines. Blood 1997;90: 3204-3213.
8. Dickinson AM, Middleton PG, Rocha V et al. Genetic polymorphisms predicting the outcome of bone marrow transplants. Br J Haematol 2004;127:479-490.
9. Shlomchik WD, Couzens MS, Tang CB et al. Prevention of graft versus host disease by inactivation of host antigen-presenting cells. Science 1999;285:412-415.
10. Matte CC, Liu J, Cormier J et al. Donor APCs are required for maximal GVHD but not for GVL. Nat Med 2004;10:987-992.
11. Lee SJ, Klein J, Haagenson M et al. High- resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood 2007;110: 4576-4583.
12. Ferrara JL, Levine JE, Reddy P et al. Graftversus-host disease. Lancet 2009;373:1550-1561.
13. Goulmy E, Schipper R, Pool J et al. Mismatches of minor histocompatibility antigens between HLA-identical donors and recipients and the development of graft-versus-host disease after bone marrow transplantation. N Engl J Med 1996;334:281-285.
14. Bleakley M, Riddell SR. Exploiting T cells specific for human minor histocompatibility antigens for therapy of leukemia. Immunol Cell Biol 2011;89:396-407.
15. Kwon B. Intervention with costimulatory pathways as a therapeutic approach for graftversus-host disease. Exp Mol Med 2010;42: 675-683.
16. Zhang Y, Joe G, Hexner E et al. Host-reactive CD8 memory stem cells in graft-versushost disease. Nat Med 2005;11:1299-1305.
17. Chen BJ, Deoliveira D, Cui X et al. Inability of memory T cells to induce graft-versus-host disease is a result of an abortive alloresponse. Blood 2007;109:3115-3123.
18. Yi T, Chen Y, Wang L et al. Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease. Blood 2009;114:3101-3112.
19. Wysocki CA, Panoskaltsis-Mortari A, Blazar BR et al. Leukocyte migration and graft-versus-host disease. Blood 2005;105: 4191-4199.
20. Dutt S, Ermann J, Tseng D et al. L-selectin and beta7 integrin on donor CD4 T cells are required for the early migration to host mesenteric lymph nodes and acute colitis of graft-versus-host disease. Blood 2005;106: 4009-4015.
21. Palmer LA, Sale GE, Balogun JI et al. Chemokine receptor CCR5 mediates alloimmune responses in graft-versus-host disease. Biol Blood Marrow Transplant 2010;16:311-319.
22. Weninger W, von Andrian UH. Chemokine regulation of naive T cell traffic in health and disease. Semin Immunol 2003;15:257-270.
23. Varona R, Cadenas V, Gomez L et al. CCR6 regulates CD4 T-cell-mediated acute graftversus-host disease responses. Blood 2005; 106:18-26.
24. Braun MY, Lowin B, French L et al. Cytotoxic T cells deficient in both functional fas ligand and perforin show residual cytolytic activity yet lose their capacity to induce lethal acute graft-versus-host disease. J Exp Med 1996;183: 657-661.
25. Schmaltz C, Alpdogan O, Kappel BJ et al. T cells require TRAIL for optimal graft-versus-tumor activity. Nat Med 2002;8:1433-1437.
26. Rowe V, Banovic T, MacDonald KP et al. Host B cells produce IL-10 following TBI and attenuate acute GVHD after allogeneic bone marrow transplantation. Blood 2006;108: 2485-2492.
27. von Bergwelt-Baildon MS, Vonderheide RH, Maecker B et al. Human primary and memory cytotoxic T lymphocyte responses are efficiently induced by means of CD40-activated B cells as antigen-presenting cells: Potential for clinical application. Blood 2002;99:3319-3325.
28. Miklos DB, Kim HT, Zorn E et al. Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in healthy female donors. Blood 2004;103:353-359.
29. Iori AP, Torelli GF, De Propris MS et al. B-cell concentration in the apheretic product predicts acute graft-versus-host disease and treatment-related mortality of allogeneic peripheral blood stem cell transplantation. Transplantation 2008;85:386-390.
30. Sarantopoulos S, Stevenson KE, Kim HT et al. Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease. Blood 2009;113:3865-3874.
31. Khouri IF, McLaughlin P, Saliba RM et al. Eight-year experience with allogeneic stem cell transplantation for relapsed follicular lymphoma after nonmyeloablative conditioning with fludarabine, cyclophosphamide, and rituximab. Blood 2008;111:5530-5536.
32. Schultz KR, Paquet J, Bader S et al. Requirement for B cells in T cell priming to minor histocompatibility antigens and development of graft-versus-host disease. Bone Marrow Transplant 1995;16:289-295.
33. Li H, Demetris AJ, McNiff J et al. Profound depletion of host conventional dendritic cells, plasmacytoid dendritic cells, and B cells does not prevent graft-versus-host disease induction. J Immunol 2012;188:3804-3811.
34. Hess AD. Reconstitution of self-tolerance after hematopoietic stem cell transplantation. Immunol Res 2010;47:143-152.
35. Holländer GA, Widmer B, Burakoff SJ. Loss of normal thymic repertoire selection and persistence of autoreactive T cells in graft vs host disease. J Immunol 1994;152: 1609-1617.
36. Beres AJ, Haribhai D, Chadwick AC et al. CD8 Foxp3 regulatory T cells are induced during graft-versus-host disease and mitigate disease severity. J Immunol 2012;189:464-474.
37. Martin PJ, Schoch G, Fisher L et al. A retrospective analysis of therapy for acute graftversus-host disease: Initial treatment. Blood 1990;76:1464-1472.
38. Darmstadt GL, Donnenberg AD, Vogelsang GB et al. Clinical, laboratory, and histopathologic indicators of the development of progressive acute graft-versus-host disease. J Invest Dermatol 1992;99:397-402.
39. Snover DC, Weisdorf SA, Vercellotti GM et al. A histopathologic study of gastric and small intestinal graft-versus-host disease following allogeneic bone marrow transplantation. Hum Pathol 1985;16:387-392.
40. Snover DC, Weisdorf SA, Ramsay NK et al. Hepatic graft versus host disease: A study of the predictive value of liver biopsy in diagnosis. Hepatology 1984;4:123-130.
41. Sullivan K. Graft-vs.-host disease. In: Blume KG FS, Appelbaum FR, ed. Thomas' Hematopoietic Cell Transplantation. 3rd ed. Oxford, U.K.: Blackwell Publishing, 2004; 635-64.
42. Paczesny S, Braun TM, Levine JE et al. Elafin is a biomarker of graft-versus-host disease of the skin. Sci Transl Med 2010;2: 13ra2.
43. Ferrara JL, Harris AC, Greenson JK et al. Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft-versus-host disease. Blood 2011;118:6702-6708.
44. Levine JE, Logan BR, Wu J et al. Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: A Blood and Marrow Transplant Clinical Trials Network study. Blood 2012;119: 3854-3860.
45. Glucksberg H, Storb R, Fefer A et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974;18:295-304.
46. Rowlings PA, Przepiorka D, Klein JP et al. IBMTR Severity Index for grading acute graftversus-host disease: Retrospective comparison with Glucksberg grade. Br J Haematol 1997;97:855-864.
47. Cahn JY, Klein JP, Lee SJ et al. Prospective evaluation of 2 acute graft-versus-host (GVHD) grading systems: A joint Societe Francaise de Greffe de Moelle et Therapie Cellulaire (SFGM-TC), Dana Farber Cancer Institute (DFCI), and International Bone Marrow Transplant Registry (IBMTR) prospective study. Blood 2005; 106:1495-1500.
48. Flowers ME, Inamoto Y, Carpenter PA et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood 2011;117:3214-3219.
49. Flowers ME, Pepe MS, Longton G et al. Previous donor pregnancy as a risk factor for acute graft-versus-host disease in patients with aplastic anaemia treated by allogeneic marrow transplantation. Br J Haematol 1990; 74:492-496.
50. van Rood JJ, Loberiza FR, Jr., Zhang MJ et al. Effect of tolerance to noninherited ma- ternal antigens on the occurrence of graft- versus-host disease after bone marrow transplantation from a parent or an HLA- haploidentical sibling. Blood 2002;99:1572-1577.
51. Gluckman E, Rocha V, Boyer-Chammard A et al. Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group. N Engl J Med 1997;337:373-381.
52. Mielcarek M, Martin PJ, Leisenring W et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 2003;102: 756-762.
53. Svenberg P, Mattsson J, Ringden O et al. Allogeneic hematopoietic SCT in patients with non-malignant diseases, and importance of chimerism. Bone Marrow Transplant 2009;44: 757-763.
54. Dey BR, McAfee S, Colby C et al. Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-versus-host disease, and antitumor response in patients with advanced hematologic malignancies treated with nonmyeloablative conditioning and allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 2003;9:320-329.
55. Bader P, Kreyenberg H, Hoelle W et al. Increasing mixed chimerism is an important prognostic factor for unfavorable outcome in children with acute lymphoblastic leukemia after allogeneic stem-cell transplantation: Possible role for pre-emptive immunotherapy? J Clin Oncol 2004;22:1696-1705.
56. van Bekkum DW, Roodenburg J, Heidt PJ et al. Mitigation of secondary disease of allogeneic mouse radiation chimeras by modification of the intestinal microflora. J Natl Cancer Inst 1974;52:401-404.
57. Beelen DW, Elmaagacli A, Muller KD et al. Influence of intestinal bacterial decontamination using metronidazole and ciprofloxacin or ciprofloxacin alone on the development of acute graft-versus-host disease after marrow transplantation in patients with hematologic malignancies: Final results and long-term follow-up of an open-label prospective randomized trial. Blood 1999; 93:3267-3275.
58. Hahn T, McCarthy PL, Jr., Zhang MJ et al. Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia. J Clin Oncol 2008;26:5728-5734.
59. Uphoff DE. Alteration of homograft reaction by A-methopterin in lethally irradiated mice treated with homologous marrow. Proc Soc Exp Biol Med 1958;99:651-653.
60. Luznik L, Fuchs EJ. High-dose, post-transplantation cyclophosphamide to promote graft-host tolerance after allogeneic hematopoietic stem cell transplantation. Immunol Res 2010;47:65-77.
61. Storb R, Antin JH, Cutler C. Should methotrexate plus calcineurin inhibitors be considered standard of care for prophylaxis of acute graft-versus-host disease? Biol Blood Marrow Transplant 2010;16:S18-S27.
62. Laskin BL, Goebel J, Davies SM et al. Small vessels, big trouble in the kidneys and beyond: Hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Blood 2011;118:1452-1462.
63. Wong R, Beguelin GZ, de Lima M et al. Tacrolimus-associated posterior reversible encephalopathy syndrome after allogeneic haematopoietic stem cell transplantation. Br J Haematol 2003;122:128-134.
64. Cutler C, Antin JH. Sirolimus immunosuppression for graft-versus-host disease prophylaxis and therapy: An update. Curr Opin Hematol 2010;17:500-504.
65. Nash RA, Johnston L, Parker P et al. A phase I/II study of mycophenolate mofetil in combination with cyclosporine for prophylaxis of acute graft-versus-host disease after myelo- ablative conditioning and allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2005;11:495-505.
66. Reshef R, Luger SM, Hexner EO et al. Blockade of lymphocyte chemotaxis in visceral graft-versus-host disease. N Engl J Med 2012; 367:135-145.
67. Antin JH, Weisdorf D, Neuberg D et al. Interleukin-1 blockade does not prevent acute graft-versus-host disease: Results of a randomized, double-blind, placebo-controlled trial of interleukin-1 receptor antagonist in allogeneic bone marrow transplantation. Blood 2002; 100:3479-3482.
68. Hamadani M, Hofmeister CC, Jansak B et al. Addition of infliximab to standard acute graft-versus-host disease prophylaxis following allogeneic peripheral blood cell transplantation. Biol Blood Marrow Transplant 2008;14: 783-789.
69. 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;10:178-185.
70. Levine JE, Blazar BR, DeFor T et al. Longterm follow-up of a phase I/II randomized, placebo-controlled trial of palifermin to prevent graft-versus-host disease (GVHD) after related donor allogeneic hematopoietic cell transplantation (HCT). Biol Blood Marrow Transplant 2008;14:1017-1021.
71. Wagner JE, Thompson JS, Carter SL et al. Effect of graft-versus-host disease prophylaxis on 3-year disease-free survival in recipients of unrelated donor bone marrow (T-cell Depletion Trial): A multi-centre, randomised phase II-III trial. Lancet 2005;366:733-741.
72. Mitsuyasu RT, Champlin RE, Gale RP et al. 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 1986;105:20-26.
73. Devine SM, Carter S, Soiffer RJ et al. Low risk of chronic graft-versus-host disease and relapse associated with T cell-depleted peripheral blood stem cell transplantation for acute myelogenous leukemia in first remission: Results of the blood and marrow transplant clinical trials network protocol 0303. Biol Blood Marrow Transplant 2011;17:1343-1351.
74. Jakubowski AA, Small TN, Kernan NA et al. T cell-depleted unrelated donor stem cell transplantation provides favorable diseasefree survival for adults with hematologic malignancies. Biol Blood Marrow Transplant 2011; 17:1335-1342.
75. Rizzieri DA, Koh LP, Long GD et al. Partially matched, nonmyeloablative allogeneic transplantation: Clinical outcomes and immune reconstitution. J Clin Oncol 2007;25: 690-697.
76. Guinan EC, Boussiotis VA, Neuberg D et al. Transplantation of anergic histoincompatible bone marrow allografts. N Engl J Med 1999;340:1704-1714.
77. Kuzmina LA, Petinati NA, Parovichnikova EN et al. Multipotent mesenchymal stromal cells for the prophylaxis of acute graft-versushost disease: A phase II study. Stem Cells Int 2012;2012:968213.
78. Thomas E, Storb R, Clift RA et al. Bonemarrow transplantation. New Engl J Med 1975; 292:832-843, 895-902.
79. Van Lint MT, Uderzo C, Locasciulli A et al. Early treatment of acute graft-versus-host disease with highor low-dose 6-methylprednisolone: A multicenter randomized trial from the Italian Group for Bone Marrow Transplantation. Blood 1998;92:2288-2293.
80. MacMillan ML, Weisdorf DJ, Wagner JE et al. Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: Comparison of grading systems. Biol Blood Marrow Transplant 2002;8:387-394.
81. Sullivan KM, Kopecky KJ, Jocom J et al. Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation. N Engl J Med 1990;323: 705-712.
82. Brunstein CG, Miller JS, Cao Q et al. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: Safety profile and detection kinetics. Blood 2011;117:1061-1070.
83. Perfetti P, Carlier P, Strada P et al. Extracorporeal photopheresis for the treatment of steroid refractory acute GVHD. Bone Marrow Transplant 2008;42:609-617.
84. Shaughnessy PJ, Bolwell BJ, van Besien K et al. Extracorporeal photopheresis for the prevention of acute GVHD in patients undergoing standard myeloablative conditioning and allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2010;45:1068-1076.
85. Shaughnessy PJ, Bachier C, Grimley M et al. Denileukin diftitox for the treatment of steroid-resistant acute graft-versus-host disease. Biol Blood Marrow Transplant 2005;11:188-193.
86. Bolaños-Meade J, Jacobsohn DA, Margolis J et al. Pentostatin in steroid-refractory acute graft-versus-host disease. J Clin Oncol 2005;23:2661-2668.
87. Furlong T, Leisenring W, Storb R et al. Psoralen and ultraviolet A irradiation (PUVA) as therapy for steroid-resistant cutaneous acute graft-versus-host disease. Biol Blood Marrow Transplant 2002;8:206-212.
88. Hockenbery DM, Cruickshank S, Rodell TC et al. A randomized, placebo-controlled trial of oral beclomethasone dipropionate as a prednisone-sparing therapy for gastrointestinal graft-versus-host disease. Blood 2007;109: 4557-4563.
89. Kebriaei P, Isola L, Bahceci E et al. Adult human mesenchymal stem cells added to corticosteroid therapy for the treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant 2009;15:804-811.
90. Le Blanc K, Frassoni F, Ball L et al. Mesenchymal stem cells for treatment of steroidresistant, severe, acute graft-versus-host disease: A phase II study. Lancet 2008;371: 1579-1586.
91. Ippoliti C, Champlin R, Bugazia N et al. Use of octreotide in the symptomatic management of diarrhea induced by graft-versus-host disease in patients with hematologic malignancies. J Clin Oncol 1997;15:3350-3354.
92. Bucher C, Koch L, Vogtenhuber C et al. IL-21 blockade reduces graft-versus-host disease mortality by supporting inducible T regulatory cell generation. Blood 2009;114:5375-5384.
93. Hanash AM, Kappel LW, Yim NL et al. Abrogation of donor T-cell IL-21 signaling leads to tissue-specific modulation of immunity and separation of GVHD from GVL. Blood 2011; 118:446-455.
94. Wang L, Tao R, Hancock WW. Using histone deacetylase inhibitors to enhance Foxp3() regulatory T-cell function and induce allograft tolerance. Immunol Cell Biol 2009;87: 195-202.
95. Taylor PA, Panoskaltsis-Mortari A, Freeman GJ et al. Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down- regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM). Blood 2005;105:3372-3380.
96. Kwan WH, Hashimoto D, Paz-Artal E et al. Antigen-presenting cell-derived complement modulates graft-versus-host disease. J Clin invest 2012;122:2234-2238.
97. Hashimoto D, Chow A, Greter M et al. Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation. J Exp Med 2011;208:1069-1082.