Biology of Blood and Marrow Transplantation
Volume 15, Issue 1, Supplement , Pages e1-e7 , January 2009

Genomic and Proteomic Analysis of Allogeneic Hematopoietic Cell Transplant Outcome. Seeking Greater Understanding the Pathogenesis of GVHD and Mortality

  • John A. Hansen

      Affiliations

    • Corresponding Author InformationCorrespondence and reprint requests: John A. Hansen, MD, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, D2-100, P.O. Box 19024, Seattle, WA 98109-1024.

References 

  1. Hansen JA, Petersdorf EW, Lin MT, et al. Genetics of allogeneic hematopoietic cell transplantation. Role of HLA matching, functional variation in immune response genes. Immunol Res. 2008;41:56–78
  2. Elkins WL. Cellular immunology and the pathogenesis of graft versus host reactions (review). Prog Allergy. 1971;15:78–187
  3. Snell GD, Dausset J, Nathenson S. Histocompatibility. New York: Academic Press; 1976;
  4. Perreault C, Décary F, Brochu S, Gyger M, Bélanger R, Roy D. Minor histocompatibility antigens. Blood. 1990;76:1269–1280
  5. Martin PJ. Increased disparity for minor histocompatibility antigens as a potential cause of increased GVHD risk in marrow transplantation from unrelated donors compared with related donors. Bone Marrow Transplant. 1991;8:217–223
  6. 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
  7. 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;11:945–956
  8. Nash RA, Pepe MS, Storb R, et al. Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate. Blood. 1992;80:1838–1845
  9. Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–828
  10. Stewart BL, Storer B, Storek J, et al. Duration of immunosuppressive treatment for chronic graft-versus-host disease. Blood. 2004;104:3501–3506
  11. Martin PJ, McDonald GB, Sanders JE, et al. Increasingly frequent diagnosis of acute gastrointestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2004;10:320–327
  12. Przepiorka D, Smith TL, Folloder J, et al. Risk factors for acute graft-versus-host disese after allogeneic blood stem cell transplantation. Blood. 1999;94:1465–1470
  13. 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
  14. Beilhack A, Schulz S, Baker J, et al. In vivo analyses of early events in acute graft-versus-host disease reveal sequential infiltration of T-cell subsets. Blood. 2005;106:1113–1122
  15. Nestel FP, Price KS, Seemayer TA, Lapp WS. Macrophage priming and lipopolysaccharide-triggered release of tumor necrosis factor α during graft-versus-host disease. J Exp Med. 1992;175:405–413
  16. Ferrara JLM, Deeg HJ. Graft-versus-host disease (review). N Engl J Med. 1991;324:667–674
  17. Antin JH, Ferrara JLM. Cytokine dysregulation and acute graft-versus-host disease. Blood. 1992;80:2964–2968
  18. Jadus MR, Websic HT. The role of cytokines in graft-versus-host reactions and disease. Bone Marrow Transplant. 1992;10:1–14
  19. Holler E, Kolb HJ, Mittermuller J, et al. Modulation of acute graft-versus-host-disease after allogeneic bone marrow transplantation by tumor necrosis factor alpha (TNF alpha) release in the course of pretransplant conditioning: role of conditioning regimens and prophylactic application of a monoclonal antibody neutralizing human TNF alpha (MAK 195F). Blood. 1995;86:890–899
  20. Krenger W, Hill GR, Ferrara JL. Cytokine cascades in acute graft-versus-host disease (review). Transplantation. 1997;64:553–558
  21. Middleton PG, Taylor PRA, Jackson G, Proctor SJ, Dickinson AM. Cytokine gene polymorphisms associating with severe acute graft-versus-host disease in HLA-identical sibling transplants. Blood. 1998;92:3943–3948
  22. Cavet J, Middleton PG, Segall M, Noreen H, Davies SM, Dickinson AM. Recipient tumor necrosis factor-alpha and interleukin-10 gene polymorphisms associate with early mortality and acute graft-versus-host disease severity in HLA-matched sibling bone marrow transplants. Blood. 1999;94:3941–3946
  23. Socie G, Loiseau P, Tamouza R, et al. Both genetic and clinical factors predict the development of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Transplantation. 2001;72:699–706
  24. Cullup H, Dickinson AM, Jackson GH, Taylor PR, Cavet J, Middleton PG. Donor interleukin 1 receptor antagonist genotype associated with acute graft-versus-host disease in human leucocyte antigen-matched sibling allogeneic transplants. Br J Haematol. 2001;113:807–813
  25. Rocha V, Franco RF, Porcher R, et al. Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation. Blood. 2002;100:3908–3918
  26. Lin M-T, Storer B, Martin PJ, et al. Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation. N Engl J Med. 2003;349:2201–2210
  27. Cullup H, Dickinson AM, Cavet J, Jackson GH, Middleton PG. Polymorphisms of interleukin-1alpha constitute independent risk factors for chronic graft-versus-host disease after allogeneic bone marrow transplantation. Br J Haematol. 2003;122:778–787
  28. MacMillan ML, Radloff GA, Defor TE, Weisdorf DJ, Davies SM. Interleukin-1 genotype and outcome of unrelated donor bone marrow transplantation. Br J Haematol. 2003;121:597–604
  29. Mullighan C, Heatley S, Doherty K, et al. Non-HLA immunogenetic polymorphisms and the risk of complications after allogeneic hemopoietic stem-cell transplantation. Transplantation. 2004;27:587–596
  30. Keen LJ, Defor TE, Bidwell JL, Davies SM, Bradley BA, Hows JM. Interleukin-10 and tumor necrosis factor alpha region haplotypes predict transplant-related mortality after unrelated donor stem cell transplantation. Blood. 2004;103:3599–3602
  31. Karabon L, Wysoczanska B, Bogunia-Kubik K, Suchnicki K, Lange A. IL-6 and IL-10 promoter gene polymorphisms of patients and donors of allogeneic sibling hematopoietic stem cell transplants associate with the risk of acute graft-versus-host disease. Hum Immunol. 2005;66:700–710
  32. Seo KW, Kim DH, Sohn SK, et al. Protective role of interleukin-10 promoter gene polymorphism in the pathogenesis of invasive pulmonary aspergillosis after allogeneic stem cell transplantation. Bone Marrow Transplant. 2005;36:1089–1095
  33. Bogunia-Kubik K, Mlynarczewska A, Jaskula E, Lange A. The presence of IFNG 3/3 genotype in the recipient associates with increased risk for Epstein-Barr virus reactivation after allogeneic haematopoietic stem cell transplantation. Br J Haematol. 2006;132:326–332
  34. Mehta PA, Eapen M, Klein JP, et al. Interleukin-1 alpha genotype and outcome of unrelated donor haematopoietic stem cell transplantation for chronic myeloid leukaemia. Br J Haematol. 2007;137:152–157
  35. Middleton PG, Norden J, Cullup H, et al. Oestrogen receptor alpha gene polymorphism associates with occurrence of graft-versus-host disease and reduced survival in HLA-matched sib-allo BMT. Bone Marrow Transplant. 2003;32:41–47
  36. Holler E, Rogler G, Herfarth H, et al. Both donor and recipient NOD2/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation. Blood. 2004;104:889–894
  37. Lin M-T, Storer B, Martin PJ, et al. Genetic variation in the IL-10 pathway modulates severity of acute graft-versus-host disease following hematopoietic cell transplantation: synergism between IL-10 genotype of patient and IL-10 receptor β genotype of donor. Blood. 2005;106:3995–4001
  38. Cardoso SM, Defor TE, Tilley LA, Bidwell JL, Weisdorf DJ, MacMillan ML. Patient interleukin-18 GCG haplotype associates with improved survival and decreased transplant-related mortality after unrelated-donor bone marrow transplantation. Br J Haematol. 2004;126:704–710
  39. Holler E, Rogler G, Brenmoehl J, et al. Prognostic significance of NOD2/CARD15 variants in HLA-identical sibling hematopoietic stem cell transplantation: effect on long term outcome is confirmed in 2 independent cohorts and may be modulated by the type of gastrointestinal decontamination. Blood. 2006;107:4189–4193
  40. Shamim Z, Ryder LP, Heilmann C, et al. Genetic polymorphisms in the genes encoding human interleukin-7 receptor-alpha: prognostic significance in allogeneic stem cell transplantation. Bone Marrow Transplant. 2006;37:485–491
  41. Perez-Garcia A, de la CR, Roman-Gomez J, et al. CTLA-4 polymorphisms and clinical outcome after allogeneic stem cell transplantation from HLA-identical sibling donors. Blood. 2007;110:461–467
  42. Azarian M, Busson M, Lepage V, et al. Donor CTLA-4 +49 A/G∗GG genotype is associated with chronic GVHD after HLA-identical haematopoietic stem-cell transplantations. Blood. 2007;110:4623–4624
  43. MacMillan ML, Radloff GA, Kiffmeyer WR, Defor TE, Weisdorf DJ, Davies SM. High-producer interleukin-2 genotype increases risk for acute graft-versus-host disease after unrelated donor bone marrow transplantation. Transplantation. 2003;76:1758–1762
  44. Dickinson AM, Harrold JL, Cullup H. Haematopoietic stem cell transplantation: can our genes predict clinical outcome? (review). Expert Rev Mol Med. 2007;9:1–19
  45. Mullighan CG, Bardy PG. New directions in the genomics of allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2007;13:127–144
  46. Mullally A, Ritz J. Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation. Blood. 2007;109:1355–1362
  47. Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Erratum appears in Nature 2001 Aug 2;412(6846):565. Note: Szustakowki, J [corrected to Szustakowski, J]. Nature. 2001;409:860–921
  48. Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome [erratum appears in Science 2001 Jun 5;292(5523):1838]. Science. 2001;291:1304–1351
  49. Miller RD, Phillips MS, Jo I, et al. High-density single-nucleotide polymorphism maps of the human genome. Genomics. 2005;86:117–126
  50. Gabriel SB, Schaffner SF, Nguyen H, et al. The structure of haplotype blocks in the human genome. Science. 2002;296:2225–2229
  51. Matsuzaki H, Dong S, Loi H, et al. Genotyping over 100,000 SNPs on a pair of oligonucleotide arrays. Nat Methods. 2004;1:109–111
  52. Steemers FJ, Chang W, Lee G, Barker DL, Shen R, Gunderson KL. Whole-genome genotyping with the single-base extension assay. Nat Methods. 2006;3:31–33
  53. Gunderson KL, Steemers FJ, Lee G, Mendoza LG, Chee MS. A genome-wide scalable SNP genotyping assay using microarray technology. Nat Genet. 2005;37:549–554
  54. Liem LM, van Houwelingen HC, Goulmy E. Serum cytokine levels after HLA-identical bone marrow transplantation. Transplantation. 1998;66:863–871
  55. Miyamoto T, Akashi K, Hayashi S, et al. Serum concentration of the soluble interleukin-2 receptor for monitoring acute graft-versus-host disease. Bone Marrow Transplant. 1996;17:185–190
  56. Grimm J, Zeller W, Zander AR. Soluble interleukin-2 receptor serum levels after allogeneic bone marrow transplantations as a marker for GVHD. Bone Marrow Transplant. 1998;21:29–32
  57. Foley R, Couban S, Walker I, et al. Monitoring soluble interleukin-2 receptor levels in related and unrelated donor allogenic bone marrow transplantation. Bone Marrow Transplant. 1998;21:769–773
  58. Nakamura H, Komatsu K, Ayaki M, et al. Serum levels of soluble IL-2 receptor, IL-12, IL-18, and IFN-gamma in patients with acute graft-versus-host disease after allogeneic bone marrow transplantation. J Allergy Clin Immunol. 2000;106:S45–S50
  59. Visentainer JE, Lieber SR, Persoli LB, et al. Serum cytokine levels and acute graft-versus-host disease after HLA-identical hematopoietic stem cell transplantation. Exp Hematol. 2003;31:1044–1050
  60. Shaiegan M, Iravani M, Babaee GR, Ghavamzadeh A. Effect of IL-18 and sIL2R on aGVHD occurrence after hematopoietic stem cell transplantation in some Iranian patients. Transpl Immunol. 2006;15:223–227
  61. Paczesny S, Krijanovski OI, Braun TM, et al. A biomarker panel for acute graft versus host disease. Blood. 9999; prepublished online October 2, 2008; DOI 10.1182/blood-2008-07-167098-
  62. Fujii H, Cuvelier G, She K, et al. Biomarkers in newly diagnosed pediatric-extensive chronic graft-versus-host disease: a report from the Children's Oncology Group. Blood. 2008;111:3276–3285
  63. Imamura M, Hashino S, Kobayashi H, et al. Serum cytokine levels in bone marrow transplantation: synergistic interaction of interleukin-6, interferon-gamma, and tumor necrosis factor-alpha in graft-versus-host disease. Bone Marrow Transplant. 1994;13:745–751
  64. Uguccioni M, Meliconi R, Nesci S, et al. Elevated interleukin-8 serum concentrations in beta-thalassemia and graft-versus-host disease. Blood. 1993;81:2252–2256
  65. Schots R, Kaufman L, Van RI, et al. Proinflammatory cytokines and their role in the development of major transplant-related complications in the early phase after allogeneic bone marrow transplantation. Leukemia. 2003;17:1150–1156
  66. Mohty M, Blaise D, Faucher C, et al. Inflammatory cytokines and acute graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation. Blood. 2005;106:4407–4411
  67. Sakata N, Yasui M, Okamura T, Inoue M, Yumura-Yagi K, Kawa K. Kinetics of plasma cytokines after hematopoietic stem cell transplantation from unrelated donors: the ratio of plasma IL-10/sTNFR level as a potential prognostic marker in severe acute graft-versus-host disease. Bone Marrow Transplant. 2001;27:1153–1161
  68. Fujimori Y, Takatsuka H, Takemoto Y, et al. Elevated interleukin (IL)-18 levels during acute graft-versus-host disease after allogeneic bone marrow transplantation. Br J Haematol. 2000;109:652–657
  69. Luft T, Conzelmann M, Benner A, et al. Serum cytokeratin-18 fragments as quantitative markers of epithelial apoptosis in liver and intestinal graft-versus-host disease. Blood. 2007;110:4535–4542
  70. Hori T, Naishiro Y, Sohma H, et al. CCL8 is a potential molecular candidate for the diagnosis of graft-versus-host disease. Blood. 2008;111:4403–4412
  71. Piper KP, Horlock C, Curnow SJ, et al. CXCL10-CXCR3 interactions play an important role in the pathogenesis of acute graft-versus-host disease in the skin following allogeneic stem-cell transplantation. Blood. 2007;110:3827–3832
  72. Okamoto T, Takatsuka H, Fujimori Y, Wada H, Iwasaki T, Kakishita E. Increased hepatocyte growth factor in serum in acute graft-versus-host disease. Bone Marrow Transplant. 2001;28:197–200
  73. Holler E, Kolb HJ, Möller A, et al. Increased serum levels of tumor necrosis factor α precede major complications of bone marrow transplantation. Blood. 1990;75:1011–1016
  74. Smith JH, Rotterdam HZ, Christie JD, et al. Specialty conference on infectious and inflammatory diseases. Mod Pathol. 1990;3:223–233
  75. Or R, Kalinkovich A, Nagler A, et al. Soluble tumor necrosis factor (sTNF) receptors: a possible prognostic marker for bone marrow transplantation-related complications. Cytokines Mol Ther. 1996;2:243–250
  76. Kitko CL, Paczesny S, Yanik G, et al. Plasma elevations of tumor necrosis factor-receptor-1 at day 7 postallogeneic transplant correlate with graft-versus-host disease severity and overall survival in pediatric patients. Biol Blood Marrow Transplant. 2008;14:759–765
  77. Choi SW, Kitko CL, Braun T, et al. Change in plasma tumor necrosis factor receptor 1 levels in the first week after myeloablative allogeneic transplantation correlates with severity and incidence of GVHD and survival. Blood. 2008;112:1539–1542
  78. Seidel C, Ringden O, Remberger M. Increased levels of syndecan-1 in serum during acute graft-versus-host disease. Transplantation. 2003;76:423–426
  79. Stark GL, Dickinson AM, Jackson GH, Taylor PR, Proctor SJ, Middleton PG. Tumour necrosis factor receptor type II 196M/R genotype correlates with circulating soluble receptor levels in normal subjects and with graft-versus-host disease after sibling allogeneic bone marrow transplantation. Transplantation. 2003;76:1742–1749
  80. Middleton PG, Cullup H, Dickinson AM, et al. Vitamin D receptor gene polymorphism associates with graft-versus-host disease and survival in HLA-matched sibling allogeneic bone marrow transplantation. Bone Marrow Transplant. 2002;30:223–228

PII: S1083-8791(08)01119-1

doi: 10.1016/j.bbmt.2008.12.500

Biology of Blood and Marrow Transplantation
Volume 15, Issue 1, Supplement , Pages e1-e7 , January 2009

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