Biology of Blood and Marrow Transplantation
Volume 12, Issue 2 , Pages 126-137 , February 2006

Toward Biomarkers for Chronic Graft-versus-Host Disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. Biomarker Working Group Report

  • Kirk R. Schultz

      Affiliations

    • British Columbia Children’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada
    • Corresponding Author InformationCorrespondence and reprint requests: Kirk R. Schultz, MD, Pediatric Hematology/Oncology/Bone Marrow Transplant, University of British Columbia, British Columbia’s Children’s Hospital, 4480 Oak St, Room A119, Vancouver, British Columbia V6H 3V4, Canada
    • ,
  • David B. Miklos

      Affiliations

    • Stanford University Medical Center, Stanford, California
    • ,
  • Daniel Fowler

      Affiliations

    • National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland
    • ,
  • Ken Cooke

      Affiliations

    • University of Michigan Medical Center, Ann Arbor, Michigan
    • ,
  • Judith Shizuru

      Affiliations

    • Stanford University Medical Center, Stanford, California
    • ,
  • Emmanuel Zorn

      Affiliations

    • Brigham and Women’s Hospital, Harvard University, Boston, Massachusetts
    • ,
  • Ernst Holler

      Affiliations

    • University of Regensburg, Regensburg, Germany
    • ,
  • James Ferrara

      Affiliations

    • University of Michigan Medical Center, Ann Arbor, Michigan
    • ,
  • Howard Shulman

      Affiliations

    • Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington
    • ,
  • Stephanie J. Lee

      Affiliations

    • Dana-Farber Cancer Institute, Boston, Massachusetts
    • ,
  • Paul Martin

      Affiliations

    • Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington
    • ,
  • Alexandra H. Filipovich

      Affiliations

    • Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio
    • ,
  • Mary E.D. Flowers

      Affiliations

    • Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington
    • ,
  • Daniel Weisdorf

      Affiliations

    • University of Minnesota, Minneapolis, Minnesota
    • ,
  • Daniel Couriel

      Affiliations

    • M.D. Anderson Cancer Center, University of Texas, Houston, Texas
    • ,
  • Peter A. Lachenbruch

      Affiliations

    • US Food and Drug Administration, Rockville, Maryland
    • ,
  • Barbara Mittleman

      Affiliations

    • National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland
    • ,
  • Georgia B. Vogelsang

      Affiliations

    • Johns Hopkins University School of Medicine, Baltimore, Maryland
    • ,
  • Steven Z. Pavletic

      Affiliations

    • National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland

Received 10 November 2005 ,Accepted 11 November 2005.

References 

  1. Biomarkers Definitions Working Group . Biomarkers and surrogate endpoints (preferred definitions and conceptual framework) . Clin Pharmacol Ther . 2001;69:89–95
  2. The Food and Drug Modernization Act of 1997. Title 21 code of federal regulations part 314 Subpart H Section 314.500.
  3. Beatty PG , Anasetti C , Hansen JA , et al.   Marrow transplantation from unrelated donors for treatment of hematologic malignancies (effect of mismatching for one HLA locus) . Blood . 1993;81:249–253
  4. Chan GW , Gorgun G , Miller KB , et al.   Persistence of host dendritic cells after transplantation is associated with graft-versus-host disease . Biol Blood Marrow Transplant . 2003;9:170–176
  5. Remberger M , Persson U , Hauzenberger D , et al.   An association between human leucocyte antigen alleles and acute and chronic graft-versus-host disease after allogeneic haematopoietic stem cell transplantation . Br J Haematol . 2002;119:751–759
  6. Lapierre V , Auperin A , Tayebi H , et al.   Societe Francaise de Greffe de Moelle et de Therapiue Cellulaire. Increased presence of anti-HLA antibodies early after allogeneic granulocyte colony-stimulating factor-mobilized peripheral blood hematopoietic stem cell transplantation compared with bone marrow transplantation . Blood . 2002;100:1484–1489
  7. van Els CA , Bakker A , Zwinderman AH , et al.   Effector mechanisms in graft-versus-host disease in response to minor histocompatibility antigens. I. Absence of correlation with cytotoxic effector cells . Transplantation . 1990;50:62–66
  8. de Bueger M , Bakker A , Bontkes H , et al.   High frequencies of cytotoxic T cell precursors against minor histocompatibility antigens after HLA-identical BMT (absence of correlation with GVHD) . Bone Marrow Transplant . 1993;11:363–368
  9. Mutis T , Gillespie G , Schrama E , et al.   Tetrameric HLA class I-minor histocompatibility antigen peptide complexes demonstrate minor histocompatibility antigen-specific cytotoxic T lymphocytes in patients with graft-versus-host disease . Nat Med . 1999;5:839–842
  10. Gallardo D , Arostegui JI , Balas A , et al.  GvHD subcommittee of the Grupo Espanol de Trasplante Hemapoyetico (GETH)   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 donor transplantation . Br J Haematol . 2001;114:931–936
  11. 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
  12. Grumet FC , Hiraki DD , Brown BWM , et al.   CD31 mismatching affects marrow transplantation outcome . Biol Blood Marrow Transplant . 2001;7:503–512
  13. Randolph SS , Gooley TA , Warren EH , et al.   Female donors contribute to a selective graft-versus-leukemia effect in male recipients of HLA-matched, related hematopoietic stem cell transplants . Blood . 2004;103:347–352
  14. 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
  15. Kojima K , Kurokawa MS , Tanimoto K , et al.   Clonal expansion of limited T cell clonotypes in affected muscle from a patient with post-transplant polymyositis . Bone Marrow Transplant . 2002;30:467–470
  16. French LE , Alcindor T , Shapiro M , et al.   Identification of amplified clonal T cell populations in the blood of patients with chronic graft-versus-host disease (positive correlation with response to photopheresis) . Bone Marrow Transplant . 2002;30:509–515
  17. Matsutani T , Yoshioka T , Tsuruta Y , et al.   Restricted usage of T-cell receptor alpha-chain variable region (TCRAV) and T-cell receptor beta-chain variable region (TCRBV) repertoires after human allogeneic haematopoietic transplantation . Br J Haematol . 2000;109:759–769
  18. Ferrara JLM , Deeg HJ . GVHD–review article . N Engl J Med . 1991;324:667–674
  19. Facon T , Jouet JP , Noel-Walter  , et al.   Involvement of TNF-alpha secreting macrophages in lethal forms of human graft-vs-host disease . Bone Marrow Transplant . 1997;20:511–515
  20. Atkinson K . Chronic graft-versus-host disease . Bone Marrow Transplant . 1990;5:69–82
  21. Liem LM , Fibbe WE , van Houwelingen HC , et al.   Serum transforming growth factor-beta1 levels in bone marrow transplant recipients correlate with blood cell counts and chronic graft-versus-host disease . Transplantation . 1999;67:59–65
  22. Tanaka J , Imamura M , Kasai M , et al.   The important balance between cytokines derived from type 1 and type 2 helper T cells in the control of graft-vs-host disease . Bone Marrow Transplant . 1997;19:571–576
  23. Lauwerys R , Renuald JC , Houssiau FA . Inhibition of in vitro immunoglobulin production by IL-12 in murine chronic graft-vs-host disease, synergism with IL-18 . Eur J Immunol . 1998;28:2017–2024
  24. Ochs LA , Blazar SR , Roy J , et al.   Cytokine expression in human cutaneous chronic graft-vs-host disease . Bone Marrow Transplant . 1996;17:1085–1092
  25. Tanaka J , Imamura M , Kasai M , et al.   Cytokine gene expression by concanavalin A-stimulated peripheral mononuclear cell after bone marrow transplantation, an indicator of immunological abnormality due to chronic graft-vs-host disease . Bone Marrow Transplant . 1994;14:695–701
  26. Yamashita K , Choi U , Woltz PC , et al.   Severe chronic graft-versus-host disease is characterized by a preponderance of CD4+ effector memory cells relative to central memory cells . Blood . 2004;103:3986–3988
  27. Xystrakis E , Bernard I , Dejean AS , et al.   Alloreactive CD4 T lymphocytes responsible for acute and chronic graft-versus-host disease are contained within the CD45RChigh but not the CD45RClow subset . Eur J Immunol . 2004;34:408–417
  28. Biedermann BC , Sahner S , Gregor M , et al.   Endothelial injury mediated by cytotoxic T lymphocytes and loss of microvessels in chronic graft versus host disease . Lancet . 2002;359:2078–2083
  29. Patey-Mariaud de Serre N , Reijasse D , Verkarre V , et al.   Chronic intestinal graft-versus-host disease (clinical, histological and immunohistochemical analysis of 17 children) . Bone Marrow Transplant . 2002;29:223–230
  30. 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;102:1217–1223
  31. Kotani A , Ishikawa T , Matsumura Y , et al.   Correlation of peripheral blood OX40+(CD134+) T cells with chronic graft-versus-host disease in patients who underwent allogeneic hematopoietic stem cell transplantation . Blood . 2001;98:3162–3164
  32. Cavet J , Dickinson AM , Norden J , et al.   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
  33. Stark GL , Dickinson AM , Jackson GH , et al.   Tumor 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
  34. 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
  35. 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
  36. Johnson BD , Konkol MC , Truitt RL . CD25+ immunoregulatory T-cells of donor origin suppress alloreactivity after BMT . Biol Blood Marrow Transplant . 2002;8:525–535
  37. Clark FJ , Gregg R , Piper K , et al.   Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4+CD25high regulatory T cells . Blood . 2004;103:2410–2416
  38. Meignin V , de Latour RP , Zuber J , et al.   Numbers of Foxp3-expressing CD4+CD25high T cells do not correlate with the establishment of long-term tolerance after allogeneic stem cell transplantation . Exp Hematol . 2005;33:894–900
  39. Miura Y , Thoburn CJ , Bright EC , et al.   Association of Foxp3 regulatory gene expression with graft-versus-host disease . Blood . 2004;104:2187–2193
  40. Sanchez J , Casano J , Alvarez MA , et al.   Kinetic of regulatory CD25high and activated CD134+ (OX40) T lymphocytes during acute and chronic graft-versus-host disease after allogeneic bone marrow transplantation . Br J Haematol . 2004;126:697–703
  41. 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;106:2903–2911
  42. Clark FJ , Freeman L , Dzionek A , et al.   Origin and subset distribution of peripheral blood dendritic cells in patients with chronic graft-versus-host disease . Transplantation . 2003;75:221–225
  43. Waller EK , Rosenthal H , Sagar L . DC2 effect on survival following allogeneic bone marrow transplantation . Oncology (Huntingt) . 2002;1(suppl 1):19–26
  44. Arpinati M , Chirumbolo G , Urbini B , et al.   Acute graft-versus-host disease and steroid treatment impair CD11c+ and CD123+ dendritic cell reconstitution after allogeneic peripheral blood stem cell transplantation . Biol Blood Marrow Transplant . 2004;10:106–115
  45. She K , Aslanian S , Shimizu H , et al.   TLR9 responses in B cells are increased at the onset of chronic GVHD . [abstract] J Pediatr Hematol Oncol . 2005;
  46. Graze PR , Gale RP . Chronic graft versus host disease (a syndrome of disordered immunity) . Am J Med . 1979;66:611–620
  47. Shulman HM , Sullivan KM , Weiden PL , et al.   Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients . Am J Med . 1980;69:204–217
  48. Storek J , Wells D , Dawson MA , et al.   Factors influencing B lymphopoiesis after allogeneic hematopoietic cell transplantation . Blood . 2001;98:489–491
  49. Loughran TP , Sullivan K , Morton T , et al.   Value of day 100 screening studies for predicting the development of chronic graft-versus-host disease after allogeneic bone marrow transplantation . Blood . 1990;76:228–234
  50. Ratanatharathorn 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;9:505–511
  51. 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;104:2603–2606
  52. Quaranta S , Shulman H , Ahmed A , et al.   Autoantibodies in human chronic graft-versus-host disease after hematopoietic cell transplantation . Clin Immunol . 1999;91:106–116
  53. Vogelsang GB . How I treat chronic graft-versus-host disease . Blood . 2001;97:1196–1201
  54. Seder RA , Pau WE . Acquisition of lymphokine-producing phenotype by CD4+ T cells . Annu Rev Immunol . 1994;12:635–673
  55. Kook H , Goldman F , Giller R , et al.   Reconstruction of the immune system after unrelated or partially matched T-cell-depleted bone marrow transplantation in children (immunophenotypic analysis and factors affecting the speed of recovery) . Blood . 1996;88:1089–1097
  56. 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
  57. Lee S , Chong SY , Lee JW , et al.   Difference in the expression of Fas/Fas ligand and the lymphocyte subset reconstitution according to the occurrence of acute GVHD . Bone Marrow Transplant . 1997;20:883–888
  58. Drakesmith H , O’Neil D , Schneider SC , et al.   In vivo priming of T cells against cryptic determinants by dendritic cells exposed to interleukin 6 and native antigen . Proc Natl Acad Sci U S A . 1998;95:14903–14908
  59. Daneshpouy M , Socie G , Lemann M , et al.   Activated eosinophils in upper gastrointestinal tract of patients with graft-versus-host disease . Blood . 2002;99:3033–3040
  60. Jacobsohn DA , Schechter T , Seshadri R , et al.   Eosinophilia correlates with the presence or development of chronic graft-versus-host disease in children . Transplantation . 2004;77:1096–1100
  61. Zhao ZZ , Savage NW , Sugerman PB , et al.   Mast cell/T cell interactions in oral lichen planus . J Oral Pathol Med . 2002;31:189–195
  62. Izutsu KT , Schubert MM , Truelove EL , et al.   The predictive value of elevated labial saliva sodium concentration (its relation to labial gland pathology in bone marrow transplant recipients) . Hum Pathol . 1983;14:29–35
  63. Izutsu KT , Menard TW , Schubert MM , et al.   Graft versus host disease-related secretory immunoglobulin A deficiency in bone marrow transplant recipients. Findings in labial saliva . Lab Invest . 1985;52:292–297
  64. Izutsu KT , Sullivan KM , Schubert MM , et al.   Disordered salivary immunoglobulin secretion and sodium transport in human chronic graft-versus-host disease . Transplantation . 1983;35:441–446
  65. Nagler RM , Nagler A . The effect of pilocarpine on salivary constituents in patients with chronic graft-versus-host disease . Arch Oral Biol . 2001;46:689–695
  66. Miklos DB , Kim HT , Miller KH , et al.   Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission . Blood . 2005;105:2973–2978
  67. Dickinson AM , Middleton PG , Rocha V , et al.  Eurobank Members   Genetic polymorphisms predicting the outcome of bone marrow transplants . Br J Haematol . 2004;127:479–490

 This project was supported by the National Institutes of Health (NIH) National Cancer Institute, Office of the Director, Cancer Therapy Evaluation Program, Intramural Research Program and Center for Cancer Research; National Heart Lung and Blood Institute, Division of Blood Diseases and Resources; Office of Rare Diseases, NIH, Office of the Director; National Institute of Allergy and Infectious Disease, Transplantation Immunology Branch; and the Health Resources and Services Administration, Division of Transplantation and the Naval Medical Research Center, C. W. Bill Young/Department of Defense Marrow Donor Recruitment and Research Program.The opinions expressed here are those of the authors and do not represent the official position of the National Institutes of Health or the US Government.

PII: S1083-8791(05)00783-4

doi: 10.1016/j.bbmt.2005.11.010

Biology of Blood and Marrow Transplantation
Volume 12, Issue 2 , Pages 126-137 , February 2006

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