Biology of Blood and Marrow Transplantation
Volume 13, Issue 2 , Pages 127-144 , February 2007

New Directions in the Genomics of Allogeneic Hematopoietic Stem Cell Transplantation

  • Charles G. Mullighan

      Affiliations

    • Pathology, St Jude Children’s Research Hospital, Memphis, Tennessee
    • Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, Australia
    • Corresponding Author InformationCorrespondence and reprint requests: Charles Mullighan, MD, Pathology, MS 342, St Jude Children’s Research Hospital, 332 N Lauderdale, Memphis, TN 38105
    • ,
  • Peter G. Bardy

      Affiliations

    • Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, Australia
    • Department of Haematology and Oncology, The Queen Elizabeth Hospital, Adelaide, Australia

Received 12 September 2006 ,Accepted 10 October 2006.

References 

  1. Loberiza F. The 2003 BMT summary slides with guide. IBMTR/ABMTR Newslett. 2003;7–10
  2. Gratwohl A, Brand R, Frassoni F, et al. Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: an EBMT analysis of lethal infectious complications and changes over calendar time. Bone Marrow Transplant. 2005;36:757–769
  3. 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
  4. Mickelson EM, Petersdorf E, Anasetti C, Martin P, Woolfrey A, Hansen JA. HLA matching in hematopoietic cell transplantation. Hum Immunol. 2000;61:92–100
  5. Billingham RE. The biology of graft-versus-host reactions. Harvey Lect. 1966;62:21–78
  6. Petersdorf EW, Malkki M. Human leukocyte antigen matching in unrelated donor hematopoietic cell transplantation. Semin Hematol. 2005;42:76–84
  7. Petersdorf EW, Gooley TA, Anasetti C, et al. Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient. Blood. 1998;92:3515–3520
  8. Ferrara JL, Reddy P. Pathophysiology of graft-versus-host disease. Semin Hematol. 2006;43:3–10
  9. 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;104:1923–1930
  10. Petersdorf EW, Anasetti C, Martin PJ, et al. Limits of HLA mismatching in unrelated hematopoietic cell transplantation. Blood. 2004;104:2976–2980
  11. Mullighan CG, Petersdorf EW. Genomic polymorphism and allogeneic hematopoietic transplantation outcome. Biol Blood Marrow Transplant. 2006;12:19–27
  12. Goulmy E. Human minor histocompatibility antigens. Curr Opin Immunol. 1996;8:75–81
  13. Marijt WA, Heemskerk MH, Kloosterboer FM, et al. Hematopoiesis-restricted minor histocompatibility antigens HA-1- or HA-2-specific T cells can induce complete remissions of relapsed leukemia. Proc Natl Acad Sci USA. 2003;100:2742–2747
  14. Chao NJ. Minors come of age: minor histocompatibility antigens and graft-versus-host disease. Biol Blood Marrow Transplant. 2004;10:215–223
  15. Goulmy E. Minor histocompatibility antigens: from transplantation problems to therapy of cancer. Hum Immunol. 2006;67:433–438
  16. den Haan JM, Meadows LM, Wang W, et al. The minor histocompatibility antigen HA-1: a diallelic gene with a single amino acid polymorphism. Science. 1998;279:1054–1057
  17. 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
  18. Tseng LH, Lin MT, Hansen JA, et al. Correlation between disparity for the minor histocompatibility antigen HA-1 and the development of acute graft-versus-host disease after allogeneic marrow transplantation. Blood. 1999;94:2911–2914
  19. Lin MT, Gooley T, Hansen JA, et al. Absence of statistically significant correlation between disparity for the minor histocompatibility antigen-HA-1 and outcome after allogeneic hematopoietic cell transplantation. Blood. 2001;98:3172–3173
  20. Balduini CL, Frassoni F, Noris P, et al. Donor-recipient incompatibility at CD31-codon 563 is a major risk factor for acute graft-versus-host disease after allogeneic bone marrow transplantation from a human leucocyte antigen-matched donor. Br J Haematol. 2001;114:951–953
  21. Perez-Garcia A, De la Camara R, Torres A, Gonzalez M, Jimenez A, Gallardo D. Minor histocompatibility antigen HA-8 mismatch and clinical outcome after HLA-identical sibling donor allogeneic stem cell transplantation. Haematologica. 2005;90:1723–1724
  22. Tait BD, Maddison R, McCluskey J, et al. Clinical relevance of the minor histocompatibility antigen HA-1 in allogeneic bone marrow transplantation between HLA identical siblings. Transplant Proc. 2001;33:1760–1761
  23. 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
  24. Kogler G, Middleton PG, Wilke M, et al. Recipient cytokine genotypes for TNF-alpha and IL-10 and the minor histocompatibility antigens HY and CD31 codon 125 are not associated with occurrence or severity of acute GVHD in unrelated cord blood transplantation: a retrospective analysis. Transplantation. 2002;74:1167–1175
  25. Heinemann FM, Ferencik S, Ottinger HD, Beelen DW, Grosse-Wilde H. Impact of disparity of minor histocompatibility antigens HA-1, CD31, and CD49b in hematopoietic stem cell transplantation of patients with chronic myeloid leukemia with sibling and unrelated donors. Transplantation. 2004;77:1103–1106
  26. Behar E, Chao NJ, Hiraki DD, et al. Polymorphism of adhesion molecule CD31 and its role in acute graft-versus-host disease. N Engl J Med. 1996;334:286–291
  27. Nichols WC, Antin JH, Lunetta KL, et al. Polymorphism of adhesion molecule CD31 is not a significant risk factor for graft-versus-host disease. Blood. 1996;88:4429–4434
  28. Maruya E, Saji H, Seki S, et al. Evidence that CD31, CD49b, and CD62L are immunodominant minor histocompatibility antigens in HLA identical sibling bone marrow transplants. Blood. 1998;92:2169–2176
  29. Cavanagh G, Chapman CE, Carter V, Dickinson AM, Middleton PG. Donor CD31 genotype impacts on transplant complications after human leukocyte antigen-matched sibling allogeneic bone marrow transplantation. Transplantation. 2005;79:602–605
  30. Katagiri T, Shiobara S, Nakao S, et al. Mismatch of minor histocompatibility antigen contributes to a graft-versus-leukemia effect rather than to acute GVHD, resulting in long-term survival after HLA-identical stem cell transplantation in Japan. Bone Marrow Transplant. 2006;38:681–686
  31. Goulmy E. Minor histocompatibility antigens: allo target molecules for tumor-specific immunotherapy. Cancer J. 2004;10:1–7
  32. Brickner AG, Evans AM, Mito JK, et al. The PANE1 gene encodes a novel human minor histocompatibility antigen that is selectively expressed in B-lymphoid cells and B-CLL. Blood. 2006;107:3779–3786
  33. Slager EH, Honders MW, van der Meijden ED, et al. Identification of the angiogenic endothelial-cell growth factor-1/thymidine phosphorylase as a potential target for immunotherapy of cancer. Blood. 2006;107:4954–4960
  34. Kircher B, Wolf M, Stevanovic S, et al. Hematopoietic lineage-restricted minor histocompatibility antigen HA-1 in graft-versus-leukemia activity after donor lymphocyte infusion. J Immunother. 2004;27:156–160
  35. Dickinson AM, Wang XN, Sviland L, et al. In situ dissection of the graft-versus-host activities of cytotoxic T cells specific for minor histocompatibility antigens. Nat Med. 2002;8:410–414
  36. Fontaine P, Roy-Proulx G, Knafo L, Baron C, Roy DC, Perreault C. Adoptive transfer of minor histocompatibility antigen-specific T lymphocytes eradicates leukemia cells without causing graft-versus-host disease. Nat Med. 2001;7:789–794
  37. Hill GR, Crawford JM, Cooke KR, Brinson YS, Pan L, Ferrara JL. Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines. Blood. 1997;90:3204–3213
  38. Cooke KR, Olkiewicz K, Erickson N, Ferrara JL. The role of endotoxin and the innate immune response in the pathophysiology of acute graft versus host disease. J Endotoxin Res. 2002;8:441–448
  39. 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;95:2754–2759
  40. Antin JH, Ferrara JL. Cytokine dysregulation and acute graft-versus-host disease. Blood. 1992;80:2964–2968
  41. Hattori K, Hirano T, Miyajima H, et al. Differential effects of anti-Fas ligand and anti-tumor necrosis factor alpha antibodies on acute graft-versus-host disease pathologies. Blood. 1998;91:4051–4055
  42. Cooke KR, Hill GR, Crawford JM, et al. Tumor necrosis factor- alpha production to lipopolysaccharide stimulation by donor cells predicts the severity of experimental acute graft-versus-host disease. J Clin Invest. 1998;102:1882–1891
  43. Allen MJ, Laederach A, Reilly PJ, Mason RJ. Polysaccharide recognition by surfactant protein d: novel interactions of a C-type lectin with nonterminal glucosyl residues. Biochemistry. 2001;40:7789–7798
  44. Xun CQ, Thompson JS, Jennings CD, Brown SA, Widmer MB. Effect of total body irradiation, busulfan-cyclophosphamide, or cyclophosphamide conditioning on inflammatory cytokine release and development of acute and chronic graft-versus-host disease in H-2-incompatible transplanted SCID mice. Blood. 1994;83:2360–2367
  45. Holler E, Ertl B, Hintermeier-Knabe R, et al. Inflammatory reactions induced by pretransplant conditioning—an alternative target for modulation of acute GvHD and complications following allogeneic bone marrow transplantation?. Leuk Lymphoma. 1997;25:217–224
  46. Remberger M, Ringden O, Markling L. TNF alpha levels are increased during bone marrow transplantation conditioning in patients who develop acute GVHD. Bone Marrow Transplant. 1995;15:99–104
  47. 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
  48. Imamura M, Hashino S, Kobayashi S, et al. Hyperacute graft-versus-host disease accompanied by increased serum interleukin-6 levels. Int J Hematol. 1994;60:85–89
  49. Imamura M, Tanaka J, Hashino S, et al. Cytokines involved in graft-versus-host disease. Hokkaido Igaku Zasshi. 1994;69:1348–1353
  50. Takatsuka H, Takemoto Y, Okada M, et al. Changes of cytokines during the course of graft-versus-host disease following bone marrow transplantation: a case report. Cytokine. 2000;12:1225–1227
  51. Holler E, Kolb HJ, Moller A, et al. Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation. Blood. 1990;75:1011–1016
  52. Holler E, Kolb HJ, Hintermeier-Knabe R, et al. Role of tumor necrosis factor alpha in acute graft-versus-host disease and complications following allogeneic bone marrow transplantation. Transplant Proc. 1993;25:1234–1236
  53. Kayaba H, Hirokawa M, Watanabe A, et al. Serum markers of graft-versus-host disease after bone marrow transplantation. J Allergy Clin Immunol. 2000;106:S40–S44
  54. Min CK, Lee WY, Min DJ, et al. The kinetics of circulating cytokines including IL-6, TNF-alpha, IL-8 and IL-10 following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2001;28:935–940
  55. Remberger M, Jaksch M, Uzunel M, Mattsson J. Serum levels of cytokines correlate to donor chimerism and acute graft-vs.-host disease after haematopoietic stem cell transplantation. Eur J Haematol. 2003;70:384–391
  56. 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
  57. 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
  58. Kami M, Matsumura T, Tanaka Y, et al. Serum levels of soluble interleukin-2 receptor after bone marrow transplantation: a true marker of acute graft-versus-host disease. Leuk Lymphoma. 2000;38:533–540
  59. 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
  60. Niederwieser D, Herold M, Woloszczuk W, et al. Endogenous IFN-gamma during human bone marrow transplantation (Analysis of serum levels of interferon and interferon-dependent secondary messages). Transplantation. 1990;50:620–625
  61. Symington FW, Symington BE, Liu PY, Viguet H, Santhanam U, Sehgal PB. The relationship of serum IL-6 levels to acute graft-versus-host disease and hepatorenal disease after human bone marrow transplantation. Transplantation. 1992;54:457–462
  62. Abdallah AN, Boiron JM, Attia Y, Cassaigne A, Reiffers J, Iron A. Plasma cytokines in graft vs host disease and complications following bone marrow transplantation. Hematol Cell Ther. 1997;39:27–32
  63. Schots R, Kaufman L, Van Riet I, 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
  64. Holler E. Cytokines, viruses, and graft-versus-host disease. Curr Opin Hematol. 2002;9:479–484
  65. Nikolic B, Lee S, Bronson RT, Grusby MJ, Sykes M. Th1 and Th2 mediate acute graft-versus-host disease, each with distinct end-organ targets. J Clin Invest. 2000;105:1289–1298
  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. Ueno Y, Ishii M, Yahagi K, et al. Fas-mediated cholangiopathy in the murine model of graft versus host disease. Hepatology. 2000;31:966–974
  68. Middleton PG, Taylor PR, 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
  69. 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
  70. Takahashi H, Furukawa T, Hashimoto S, et al. Contribution of TNF-alpha and IL-10 gene polymorphisms to graft-versus-host disease following allo-hematopoietic stem cell transplantation. Bone Marrow Transplant. 2000;26:1317–1323
  71. Cavet J, Dickinson AM, Norden J, Taylor PR, Jackson GH, Middleton PG. Interferon-gamma and interleukin-6 gene polymorphisms associate with graft-versus-host disease in HLA-matched sibling bone marrow transplantation. Blood. 2001;98:1594–1600
  72. 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
  73. Lorenz E, Schwartz DA, Martin PJ, et al. Association of TLR4 mutations and the risk for acute GVHD after HLA-matched-sibling hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2001;7:384–387
  74. 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
  75. Tambur AR, Yaniv I, Stein J, et al. Cytokine gene polymorphism in patients with graft-versus-host disease. Transplant Proc. 2001;33:502–503
  76. Ishikawa Y, Kashiwase K, Akaza T, et al. Polymorphisms in TNFA and TNFR2 affect outcome of unrelated bone marrow transplantation. Bone Marrow Transplant. 2002;29:569–575
  77. 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
  78. Mullighan CG, Heatley S, Doherty K, et al. Mannose-binding lectin gene polymorphisms are associated with major infection following allogeneic hemopoietic stem cell transplantation. Blood. 2002;99:3524–3529
  79. Nordlander A, Uzunel M, Mattsson J, Remberger M. The TNFd4 allele is correlated to moderate-to-severe acute graft-versus-host disease after allogeneic stem cell transplantation. Br J Haematol. 2002;119:1133–1136
  80. Wang JB, Ren HY, Li D, Sun Q, Lu DP. Frequency of donor TNF-alpha gene polymorphism in patients with graft versus host disease following hematopoietic stem cell transplantation. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2002;10:133–137
  81. Bogunia-Kubik K, Polak M, Lange A. TNF polymorphisms are associated with toxic but not with aGVHD complications in the recipients of allogeneic sibling haematopoietic stem cell transplantation. Bone Marrow Transplant. 2003;32:617–622
  82. 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
  83. Lin MT, 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
  84. 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
  85. 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
  86. 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
  87. 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
  88. 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
  89. 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
  90. 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;77:587–596
  91. Mlynarczewska A, Wysoczanska B, Karabon L, Bogunia-Kubik K, Lange A. Lack of IFN-gamma 2/2 homozygous genotype independently of recipient age and intensity of conditioning regimen influences the risk of aGVHD manifestation after HLA-matched sibling haematopoietic stem cell transplantation. Bone Marrow Transplant. 2004;34:339–344
  92. Pihusch M, Lohse P, Reitberger J, et al. Impact of thrombophilic gene mutations and graft-versus-host disease on thromboembolic complications after allogeneic hematopoietic stem-cell transplantation. Transplantation. 2004;78:911–918
  93. Shaw BE, Maldonado H, Madrigal JA, et al. Polymorphisms in the TNFA gene promoter region show evidence of strong linkage disequilibrium with HLA and are associated with delayed neutrophil engraftment in unrelated donor hematopoietic stem cell transplantation. Tissue Antigens. 2004;63:401–411
  94. Srivastava A, Poonkuzhali B, Shaji RV, et al. Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation. Blood. 2004;104:1574–1577
  95. Bogunia-Kubik K, Mlynarczewska A, Wysoczanska B, Lange A. Recipient interferon-gamma 3/3 genotype contributes to the development of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Haematologica. 2005;90:425–456
  96. Bogunia-Kubik K, Lange A. HSP70-hom gene polymorphism in allogeneic hematopoietic stem-cell transplant recipients correlates with the development of acute graft-versus-host disease. Transplantation. 2005;79:815–820
  97. 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
  98. 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
  99. Kim DH, Lee NY, Sohn SK, et al. IL-10 promoter gene polymorphism associated with the occurrence of chronic GVHD and its clinical course during systemic immunosuppressive treatment for chronic GVHD after allogeneic peripheral blood stem cell transplantation. Transplantation. 2005;79:1615–1622
  100. Lin MT, 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 beta genotype of donor. Blood. 2005;106:3995–4001
  101. Onizuka M, Kasai M, Oba T, et al. Increased frequency of the angiotensin-converting enzyme gene D-allele is associated with noninfectious pulmonary dysfunction following allogeneic stem cell transplant. Bone Marrow Transplant. 2005;36:617–620
  102. 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
  103. Laguila Visentainer JE, Lieber SR, Lopes Persoli LB, et al. Relationship between cytokine gene polymorphisms and graft-versus-host disease after allogeneic stem cell transplantation in a Brazilian population. Cytokine. 2005;32:171–177
  104. Chien JW, Zhao LP, Hansen JA, Fan WH, Parimon T, Clark JG. Genetic variation in bactericidal/permeability-increasing protein influences the risk of developing rapid airflow decline after hematopoietic cell transplantation. Blood. 2006;107:2200–2207
  105. 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
  106. 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
  107. Terakura S, Murata M, Nishida T, et al. Increased risk for treatment-related mortality after bone marrow transplantation in GSTM1-positive recipients. Bone Marrow Transplant. 2006;37:381–386
  108. 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
  109. Granell M, Urbano-Ispizua A, Arostegui JI, et al. Effect of NOD2/CARD15 variants in T-cell depleted allogeneic stem cell transplantation. Haematologica. 2006;91:1372–1376
  110. Rozman P, Karas M, Kosir A, et al. Are human platelet alloantigens (HPA) minor transplantation antigens in clinical bone marrow transplantation?. Bone Marrow Transplant. 2003;31:497–506
  111. Bettens F, Passweg J, Gratwohl A, et al. Association of TNFd and IL-10 polymorphisms with mortality in unrelated hematopoietic stem cell transplantation. Transplantation. 2006;81:1261–1267
  112. Hajeer AH, Hutchinson IV. Influence of TNFalpha gene polymorphisms on TNFalpha production and disease. Hum Immunol. 2001;62:1191–1199
  113. Low AS, Azmy I, Sharaf N, Cannings C, Wilson AG. Association between two tumour necrosis factor intronic polymorphisms and HLA alleles. Eur J Immunogenet. 2002;29:31–34
  114. Spink CF, Keen LJ, Mensah FK, Law GR, Bidwell JL, Morgan GJ. Association between non-Hodgkin lymphoma and haplotypes in the TNF region. Br J Haematol. 2006;133:293–300
  115. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV. An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet. 1997;24:1–8
  116. Crawley E, Kay R, Sillibourne J, Patel P, Hutchinson I, Woo P. Polymorphic haplotypes of the interleukin-10 5′ flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis. Arthritis Rheum. 1999;42:1101–1108
  117. Suarez A, Castro P, Alonso R, Mozo L, Gutierrez C. Interindividual variations in constitutive interleukin-10 messenger RNA and protein levels and their association with genetic polymorphisms. Transplantation. 2003;75:711–717
  118. Pawlik A, Baskiewicz-Masiuk M, Machalinski B, Gawronska-Szklarz B. Association of cytokine gene polymorphisms and the release of cytokines from peripheral blood mononuclear cells treated with methotrexate and dexamethasone. Int Immunopharmacol. 2006;6:351–357
  119. Mullally A, Ritz J. Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation. Blood. 2006;doi:10.1182/blood-2006-06-030858
  120. Dickinson AM, Charron D. Non-HLA immunogenetics in hematopoietic stem cell transplantation. Curr Opin Immunol. 2005;17:517–525
  121. Dickinson AM, Middleton PG. Beyond the HLA typing age: genetic polymorphisms predicting transplant outcome. Blood Rev. 2005;19:333–340
  122. Hugot JP, Chamaillard M, Zouali H, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature. 2001;411:599–603
  123. Ogura Y, Bonen DK, Inohara N, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature. 2001;411:603–606
  124. Mullighan CG, Bardy PG. Mannose-binding lectin and infection following allogeneic hemopoietic stem cell transplantation. Leuk Lymphoma. 2004;45:247–256
  125. Worthley DL, Bardy PG, Mullighan CG. Mannose-binding lectin: biology and clinical implications. Intern Med J. 2005;35:548–555
  126. Minchinton RM, Dean MM, Clark TR, Heatley S, Mullighan CG. Analysis of the relationship between mannose-binding lectin (MBL) genotype, MBL levels and function in an Australian blood donor population. Scand J Immunol. 2002;56:630–641
  127. Horiuchi T, Gondo H, Miyagawa H, et al. Association of MBL gene polymorphisms with major bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT. Genes Immun. 2005;6:162–166
  128. Molle I, Peterslund NA, Thiel S, Steffensen R. MBL2 polymorphism and risk of severe infections in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation. Bone Marrow Transplant. 2006;38:555–560
  129. Granell M, Urbano-Ispizua A, Lozano F, et al. Donor’s mannan-binding lectin (MBL) gene polymorphism is associated with invasive fungal infection following allogeneic stem cell transplantation. Blood. 2004;104:2220
  130. Kesh S, Mensah NY, Peterlongo P, et al. TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation. Ann NY Acad Sci. 2005;1062:95–103
  131. Ulrich CM, Robien K, McLeod HL. Cancer pharmacogenetics: polymorphisms, pathways and beyond. Nat Rev Cancer. 2003;3:912–920
  132. Eichelbaum M, Ingelman-Sundberg M, Evans WE. Pharmacogenomics and individualized drug therapy. Annu Rev Med. 2006;57:119–137
  133. Bornhauser M, Storer B, Slattery JT, et al. Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells. Blood. 2003;102:820–826
  134. Bolinger AM, Zangwill AB, Slattery JT, et al. Target dose adjustment of busulfan in pediatric patients undergoing bone marrow transplantation. Bone Marrow Transplant. 2001;28:1013–1018
  135. Demirer T, Buckner CD, Appelbaum FR, et al. Busulfan, cyclophosphamide and fractionated total body irradiation for autologous or syngeneic marrow transplantation for acute and chronic myelogenous leukemia: phase I dose escalation of busulfan based on targeted plasma levels. Bone Marrow Transplant. 1996;17:491–495
  136. Pui CH, Relling MV, Evans WE. Role of pharmacogenomics and pharmacodynamics in the treatment of acute lymphoblastic leukaemia. Best Pract Res Clin Haematol. 2002;15:741–756
  137. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111–113
  138. Weisberg I, Tran P, Christensen B, Sibani S, Rozen R. A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity. Mol Genet Metab. 1998;64:169–172
  139. Ulrich CM, Yasui Y, Storb R, et al. Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism. Blood. 2001;98:231–234
  140. Robien K, Schubert MM, Bruemmer B, Lloid ME, Potter JD, Ulrich CM. Predictors of oral mucositis in patients receiving hematopoietic cell transplants for chronic myelogenous leukemia. J Clin Oncol. 2004;22:1268–1275
  141. Robien K, Ulrich CM, Bigler J, et al. Methylenetetrahydrofolate reductase genotype affects risk of relapse after hematopoietic cell transplantation for chronic myelogenous leukemia. Clin Cancer Res. 2004;10:7592–7598
  142. Robien K, Schubert MM, Chay T, et al. Methylenetetrahydrofolate reductase and thymidylate synthase genotypes modify oral mucositis severity following hematopoietic stem cell transplantation. Bone Marrow Transplant. 2006;37:799–800
  143. Kalayoglu-Besisik S, Caliskan Y, Sargin D, Gurses N, Ozbek U. Methylenetetrahydrofolate reductase C677T polymorphism and toxicity in allogeneic hematopoietic cell transplantation. Transplantation. 2003;76:1775–1777
  144. Murphy N, Diviney M, Szer J, et al. Donor methylenetetrahydrofolate reductase genotype is associated with graft-versus-host disease in hematopoietic stem cell transplant patients treated with methotrexate. Bone Marrow Transplant. 2006;37:773–779
  145. Robien K, Bigler J, Yasui Y, et al. Methylenetetrahydrofolate reductase and thymidylate synthase genotypes and risk of acute graft-versus-host disease following hematopoietic cell transplantation for chronic myelogenous leukemia. Biol Blood Marrow Transplant. 2006;12:973–980
  146. Farag SS, Fehniger TA, Ruggeri L, Velardi A, Caligiuri MA. Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect. Blood. 2002;100:1935–1947
  147. Shilling HG, McQueen KL, Cheng NW, Shizuru JA, Negrin RS, Parham P. Reconstitution of NK cell receptor repertoire following HLA-matched hematopoietic cell transplantation. Blood. 2003;101:3730–3740
  148. Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097–2100
  149. Giebel S, Locatelli F, Lamparelli T, et al. Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. Blood. 2003;102:814–819
  150. Davies SM, Ruggieri L, DeFor T, et al. Evaluation of KIR ligand incompatibility in mismatched unrelated donor hematopoietic transplants (Killer immunoglobulin-like receptor). Blood. 2002;100:3825–3827
  151. Bishara A, De Santis D, Witt CC, et al. The beneficial role of inhibitory KIR genes of HLA class I NK epitopes in haploidentically mismatched stem cell allografts may be masked by residual donor-alloreactive T cells causing GVHD. Tissue Antigens. 2004;63:204–211
  152. Bornhauser M, Schwerdtfeger R, Martin H, Frank KH, Theuser C, Ehninger G. Role of KIR ligand incompatibility in hematopoietic stem cell transplantation using unrelated donors. Blood. 2004;103:2860–2862
  153. Aversa F, Terenzi A, Tabilio A, et al. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005;23:3447–3454
  154. Schaffer M, Malmberg KJ, Ringden O, Ljunggren HG, Remberger M. Increased infection-related mortality in KIR-ligand-mismatched unrelated allogeneic hematopoietic stem-cell transplantation. Transplantation. 2004;78:1081–1085
  155. Cooley S, McCullar V, Wangen R, et al. KIR reconstitution is altered by T cells in the graft and correlates with clinical outcomes after unrelated donor transplantation. Blood. 2005;106:4370–4376
  156. Hsu KC, Chida S, Geraghty DE, Dupont B. The killer cell immunoglobulin-like receptor (KIR) genomic region: gene-order, haplotypes and allelic polymorphism. Immunol Rev. 2002;190:40–52
  157. Cook MA, Moss PA, Briggs DC. The distribution of 13 killer-cell immunoglobulin-like receptor loci in UK blood donors from three ethnic groups. Eur J Immunogenet. 2003;30:213–221
  158. Leung W, Iyengar R, Turner V, et al. Determinants of antileukemia effects of allogeneic NK cells. J Immunol. 2004;172:644–650
  159. Hsu KC, Keever-Taylor CA, Wilton A, et al. Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes. Blood. 2005;105:4878–4884
  160. Hsu KC, Gooley T, Malkki M, et al. KIR ligands and prediction of relapse after unrelated donor hematopoietic cell transplantation for hematologic malignancy. Biol Blood Marrow Transplant. 2006;12:828–836
  161. Cook MA, Milligan DW, Fegan CD, et al. The impact of donor KIR and patient HLA-C genotypes on outcome following HLA-identical sibling hematopoietic stem cell transplantation for myeloid leukemia. Blood. 2004;103:1521–1526
  162. Chen C, Busson M, Rocha V, et al. Activating KIR genes are associated with CMV reactivation and survival after non-T-cell depleted HLA-identical sibling bone marrow transplantation for malignant disorders. Bone Marrow Transplant. 2006;38:437–444
  163. Cook M, Briggs D, Craddock C, et al. Donor KIR genotype has a major influence on the rate of cytomegalovirus reactivation following T-cell replete stem cell transplantation. Blood. 2006;107:1230–1232
  164. Farag SS, Bacigalupo A, Eapen M, et al. The effect of KIR ligand incompatibility on the outcome of unrelated donor transplantation: a report from the center for international blood and marrow transplant research, the European blood and marrow transplant registry, and the Dutch registry. Biol Blood Marrow Transplant. 2006;12:876–884
  165. Dickinson AM. Biobanks and registries for HSCT research: potential for future individualized medicine. Int J Immunogenet. 2006;33:153–154
  166. Bidwell J, Keen L, Gallagher G, et al. Cytokine gene polymorphism in human disease: on-line databases, supplement 1. Genes Immun. 2001;2:61–70
  167. Kaijzel EL, Bayley JP, van Krugten MV, et al. Allele-specific quantification of tumor necrosis factor alpha (TNF) transcription and the role of promoter polymorphisms in rheumatoid arthritis patients and healthy individuals. Genes Immun. 2001;2:135–144
  168. Turner DM, Grant SC, Lamb WR, et al. A genetic marker of high TNF-alpha production in heart transplant recipients. Transplantation. 1995;60:1113–1117
  169. 14th International HLA and Immunogenetics Workshop. Available at: http://www.microbiol.unimelb.edu.au/14ihiws//. Accessed September 12, 2006.
  170. International HapMap Consortium. A haplotype map of the human genome. Nature. 2005;437:1299–1320
  171. Fan JB, Chee MS, Gunderson KL. Highly parallel genomic assays. Nat Rev Genet. 2006;7:632–644
  172. Affymetrix Microarray Bulletin; 2005. Available at: http://microarraybulletin.com/community/wp-content/uploads/2006/04/AMB_Ogawa_v1iss1.pdf. Accessed September 8, 2006.
  173. Conrad DF, Andrews TD, Carter NP, Hurles ME, Pritchard JK. A high-resolution survey of deletion polymorphism in the human genome. Nat Genet. 2006;38:75–81
  174. Da Costa L, Charron D, Loiseau P. Does the adhesion molecule CD31 act as a minor histocompatibility antigen?. Blood. 1997;90:1332
  175. Juji T, Watanabe Y, Ishikawa Y, et al. Human platelet alloantigen (HPA)-5a/b mismatch decreases disease-free survival in unrelated bone marrow transplantation. Tissue Antigens. 1999;54:229–234
  176. Akatsuka Y, Warren EH, Gooley TA, et al. Disparity for a newly identified minor histocompatibility antigen, HA-8, correlates with acute graft-versus-host disease after haematopoietic stem cell transplantation from an HLA-identical sibling. Br J Haematol. 2003;123:671–675
  177. Nesci S, Buffi O, Iliescu A, Andreani M, Lucarelli G. Recipient mHag-HA1 disparity and aGVHD in thalassemic-transplanted patients. Bone Marrow Transplant. 2003;31:575–578
  178. Nishida T, Akatsuka Y, Morishima Y, et al. Clinical relevance of a newly identified HLA-A24-restricted minor histocompatibility antigen epitope derived from BCL2A1, ACC-1, in patients receiving HLA genotypically matched unrelated bone marrow transplant. Br J Haematol. 2004;124:629–635
  179. Grumet FC, Hiraki DD, Brown BWM, et al. CD31 mismatching affects marrow transplantation outcome. Biol Blood Marrow Transplant. 2001;7(9):503–512
  180. Gallardo D, Arostegui JI, Balas A, et al. Disparity for the minor histocompatibility antigen HA-1 is associated with an increased risk of acute graft-versus-host disease (GvHD) but it does not affect chronic GvHD incidence, disease-free survival or overall survival after allogeneic human leucocyte antigen-identical sibling donar transplantation. Br J Haematol. 2001;114:931–936

PII: S1083-8791(06)00717-8

doi: 10.1016/j.bbmt.2006.10.018

Biology of Blood and Marrow Transplantation
Volume 13, Issue 2 , Pages 127-144 , February 2007

Article Tools

* Image Usage & Resolution