• 1
    Gratwohl A, Baldomero H, Aljurf M et al. Hematopoietic stem cell transplantation: A global perspective. JAMA 2010;303:16171624.
  • 2
    Gooley TA, Chien JW, Pergam SA et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med 2010;363:20912101.
  • 3
    Ferrara JL, Levine JE, Reddy P et al. Graft-versus-host disease. Lancet 2009;373:15501561.
  • 4
    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;11:945956.
  • 5
    Arnold R, Schmeiser T, Heit W et al. Hemopoietic reconstitution after bone marrow transplantation. Exp Hematol 1986;14:271277.
  • 6
    Ma DD, Varga DE, Biggs JC. Haemopoietic reconstitution after allogeneic bone marrow transplantation in man: Recovery of haemopoietic progenitors (CFU-Mix, BFU-E and CFU-GM). Br J Haematol 1987;65:510.
  • 7
    Martinez-Jaramillo G, Gomez-Morales E, Sanchez-Valle E et al. Severe hematopoietic alterations in vitro, in bone marrow transplant recipients who develop graft-versus-host disease. J Hematother Stem Cell Res 2001;10:347354.
  • 8
    Welniak LA, Blazar BR, Murphy WJ. Immunobiology of allogeneic hematopoietic stem cell transplantation. Annu Rev Immunol 2007;25:139170.
  • 9
    Storek J, Wells D, Dawson MA et al. Factors influencing B lymphopoiesis after allogeneic hematopoietic cell transplantation. Blood 2001;98:489491.
  • 10
    Bosch M, Khan FM, Storek J. Immune reconstitution after hematopoietic cell transplantation. Curr Opin Hematol 2012;19:324335.
  • 11
    Maraninchi D, Gluckman E, Blaise D et al. Impact of T-cell depletion on outcome of allogeneic bone-marrow transplantation for standard-risk leukaemias. Lancet 1987;2:175178.
  • 12
    Marmont AM, Horowitz MM, Gale RP et al. T-cell depletion of HLA-identical transplants in leukemia. Blood 1991;78:21202130.
  • 13
    Kernan NA, Bordignon C, Heller G et al. Graft failure after T-cell-depleted human leukocyte antigen identical marrow transplants for leukemia: I. Analysis of risk factors and results of secondary transplants. Blood 1989;74:22272236.
  • 14
    Martin PJ. Influence of alloreactive T cells on initial hematopoietic reconstitution after marrow transplantation. Exp Hematol 1995;23:174179.
  • 15
    Bayraktar UD, de LM, Saliba RM et al. Ex vivo T cell-depleted versus unmodified allografts in patients with acute myeloid leukemia in first complete remission. Biol Blood Marrow Transplant 2013;19:898903.
  • 16
    Pasquini MC, Devine S, Mendizabal A et al. Comparative outcomes of donor graft CD34+ selection and immune suppressive therapy as graft-versus-host disease prophylaxis for patients with acute myeloid leukemia in complete remission undergoing HLA-matched sibling allogeneic hematopoietic cell transplantation. J Clin Oncol 2012;30:31943201.
  • 17
    Muller AM, Linderman JA, Florek M et al. Allogeneic T cells impair engraftment and hematopoiesis after stem cell transplantation. Proc Natl Acad Sci USA 2010;107:1472114726.
  • 18
    Tsao GJ, Allen JA, Logronio KA et al. Purified hematopoietic stem cell allografts reconstitute immunity superior to bone marrow. Proc Natl Acad Sci USA 2009;106:32883293.
  • 19
    Pulanic D, Lozier JN, Pavletic SZ. Thrombocytopenia and hemostatic disorders in chronic graft versus host disease. Bone Marrow Transplant 2009;44:393403.
  • 20
    Akpek G, Zahurak ML, Piantadosi S et al. Development of a prognostic model for grading chronic graft-versus-host disease. Blood 2001;97:12191226.
  • 21
    Akpek G, Lee SJ, Flowers ME et al. Performance of a new clinical grading system for chronic graft-versus-host disease: A multicenter study. Blood 2003;102:802809.
  • 22
    Anasetti C, Rybka W, Sullivan KM et al. Graft-v-host disease is associated with autoimmune-like thrombocytopenia. Blood 1989;73:10541058.
  • 23
    Arora M, Burns LJ, Davies SM et al. Chronic graft-versus-host disease: A prospective cohort study. Biol Blood Marrow Transplant 2003;9:3845.
  • 24
    Arora M, Nagaraj S, Wagner JE et al. Chronic graft-versus-host disease (cGVHD) following unrelated donor hematopoietic stem cell transplantation (HSCT): Higher response rate in recipients of unrelated donor (URD) umbilical cord blood (UCB). Biol Blood Marrow Transplant 2007;13:11451152.
  • 25
    Bat T, Steinberg SM, Childs R et al. Active thrombopoiesis is associated with worse severity and activity of chronic GVHD. Bone Marrow Transplant 2013;48:15691573.
  • 26
    Bruno B, Gooley T, Sullivan KM et al. Secondary failure of platelet recovery after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2001;7:154162.
  • 27
    Dominietto A, Raiola AM, van Lint MT et al. Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: Graft-versus-host disease, donor type, cytomegalovirus infections and cell dose. Br J Haematol 2001;112:219227.
  • 28
    First LR, Smith BR, Lipton J et al. Isolated thrombocytopenia after allogeneic bone marrow transplantation: Existence of transient and chronic thrombocytopenic syndromes. Blood 1985;65:368374.
  • 29
    Kuzmina Z, Eder S, Bohm A et al. Significantly worse survival of patients with NIH-defined chronic graft-versus-host disease and thrombocytopenia or progressive onset type: Results of a prospective study. Leukemia 2012;26:746756.
  • 30
    Lee KH, Lee JH, Choi SJ et al. Failure of trilineage blood cell reconstitution after initial neutrophil engraftment in patients undergoing allogeneic hematopoietic cell transplantation—Frequency and outcomes. Bone Marrow Transplant 2004;33:729734.
  • 31
    Pavletic SZ, Smith LM, Bishop MR et al. Prognostic factors of chronic graft-versus-host disease after allogeneic blood stem-cell transplantation. Am J Hematol 2005;78:265274.
  • 32
    Peralvo J, Bacigalupo A, Pittaluga PA et al. Poor graft function associated with graft-versus-host disease after allogeneic marrow transplantation. Bone Marrow Transplant 1987;2:279285.
  • 33
    Przepiorka D, Anderlini P, Saliba R et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation. Blood 2001;98:16951700.
  • 34
    Sullivan KM, Witherspoon RP, Storb R et al. Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-v-host disease: Prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation. Blood 1988;72:546554.
  • 35
    Fujimori Y, Kanamaru A, Saheki K et al. Recombinant human erythropoietin for late-onset anemia after allogeneic bone marrow transplantation. Int J Hematol 1998;67:131136.
  • 36
    Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells 1978;4:725.
  • 37
    Mendez-Ferrer S, Michurina TV, Ferraro F et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 2010;466:829834.
  • 38
    Lo CC, Scadden DT. The haematopoietic stem cell niche at a glance. J Cell Sci 2011;124:35293535.
  • 39
    Fujisaki J, Wu J, Carlson AL et al. In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche. Nature 2011;474:216219.
  • 40
    Iwasaki T, Fujiwara H, Iwasaki T et al. Loss of proliferative capacity and T cell immune development potential by bone marrow from mice undergoing a graft-vs-host reaction. J Immunol 1986;137:31003108.
  • 41
    Chen J, Lipovsky K, Ellison FM et al. Bystander destruction of hematopoietic progenitor and stem cells in a mouse model of infusion-induced bone marrow failure. Blood 2004;104:16711678.
  • 42
    Chen J, Brandt JS, Ellison FM et al. Defective stromal cell function in a mouse model of infusion-induced bone marrow failure. Exp Hematol 2005;33:901908.
  • 43
    Mori T, Nishimura T, Ikeda Y et al. Involvement of Fas-mediated apoptosis in the hematopoietic progenitor cells of graft-versus-host reaction-associated myelosuppression. Blood 1998;92:101107.
  • 44
    Sprangers B, Van WB, Luyckx A et al. Subclinical GvHD in non-irradiated F1 hybrids: Severe lymphoid-tissue GvHD causing prolonged immune dysfunction. Bone Marrow Transplant 2011;46:586596.
  • 45
    Bloom ML, Wolk AG, Simon-Stoos KL et al. A mouse model of lymphocyte infusion-induced bone marrow failure. Exp Hematol 2004;32:11631172.
  • 46
    Piguet PF. GVHR elicited by products of class I or class II loci of the MHC: Analysis of the response of mouse T lymphocytes to products of class I and class II loci of the MHC in correlation with GVHR-induced mortality, medullary aplasia, and enteropathy. J Immunol 1985;135:16371643.
  • 47
    Sprent J, Surh CD, Agus D et al. Profound atrophy of the bone marrow reflecting major histocompatibility complex class II-restricted destruction of stem cells by CD4+ cells. J Exp Med 1994;180:307317.
  • 48
    Hirabayashi N. Studies on graft versus host (GvH) reactions. I. Impairment of hemopoietic stroma in mice suffering from GvH disease. Exp Hematol 1981;9:101110.
  • 49
    Okamoto T, Kanamaru A, Kakishita E et al. Studies of stromal fibroblastic progenitors and hematopoietic progenitors in patients with acute graft-versus-host disease. Ann N Y Acad Sci 1991;628:307309.
  • 50
    Chiu KM, Knospe WH. Inhibitor of granulocyte-macrophage colony formation in plasma of mice rendered aplastic by allogeneic lymph node cells. Exp Hematol 1989;17:335339.
  • 51
    Reddy P, Ferrara JLM. Mouse Models of Graft-Versus-Host Disease. StemBook [internet]. Cambridge, MA: Harvard Stem Cell Institute, 2008.
  • 52
    Iwasaki T, Hamano T, Saheki K et al. Effect of graft-versus-host disease (GVHD) on host hematopoietic progenitor cells is mediated by Fas-Fas ligand interactions but this does not explain the effect of GVHD on donor cells. Cell Immunol 1999;197:3038.
  • 53
    Rieger K, Marinets O, Fietz T et al. Mesenchymal stem cells remain of host origin even a long time after allogeneic peripheral blood stem cell or bone marrow transplantation. Exp Hematol 2005;33:605611.
  • 54
    Billingham RE. The biology of graft-versus-host reactions. Harvey Lect 1966;62:2178.
  • 55
    Shono Y, Ueha S, Wang Y et al. Bone marrow graft-versus-host disease: Early destruction of hematopoietic niche after MHC-mismatched hematopoietic stem cell transplantation. Blood 2010;115:54015411.
  • 56
    van Dijken PJ, Wimperis J, Crawford JM et al. Effect of graft-versus-host disease on hematopoiesis after bone marrow transplantation in mice. Blood 1991;78:27732779.
  • 57
    Garvy BA, Elia JM, Hamilton BL et al. Suppression of B-cell development as a result of selective expansion of donor T cells during the minor H antigen graft-versus-host reaction. Blood 1993;82:27582766.
  • 58
    Chewning JH, Zhang W, Randolph DA et al. Allogeneic Th1 cells home to host bone marrow and spleen and mediate IFNgamma-dependent aplasia. Biol Blood Marrow Transplant 2013;19:876887.
  • 59
    Baker MB, Riley RL, Podack ER et al. Graft-versus-host-disease-associated lymphoid hypoplasia and B cell dysfunction is dependent upon donor T cell-mediated Fas-ligand function, but not perforin function. Proc Natl Acad Sci USA 1997;94:13661371.
  • 60
    Delisle JS, Gaboury L, Belanger MP et al. Graft-versus-host disease causes failure of donor hematopoiesis and lymphopoiesis in interferon-gamma receptor-deficient hosts. Blood 2008;112:21112119.
  • 61
    Pittenger MF, Mackay AM, Beck SC et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143147.
  • 62
    Fasslrinner F, Wobus M, Duryagina R et al. Differential effects of mixed lymphocyte reaction supernatant on human mesenchymal stromal cells. Exp Hematol 2012;40:934944.
  • 63
    Chan JL, Tang KC, Patel AP et al. Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-gamma. Blood 2006;107:48174824.
  • 64
    Romieu-Mourez R, Francois M, Boivin MN et al. Regulation of MHC class II expression and antigen processing in murine and human mesenchymal stromal cells by IFN-gamma, TGF-beta, and cell density. J Immunol 2007;179:15491558.
  • 65
    Mensen A, Jöhrens K, Anagnostopoulos I et al. Acute bone marrow GvHD is associated with delayed B cell neogenesis and impaired natural antibody response after allogeneic hematopoietic stem cell transplantation. Blood 2013;122:Abstract 4605.
  • 66
    Shono Y, Shiratori S, Kosugi-Kanaya M et al. Bone marrow graft-versus-host disease: Evaluation of its clinical impact on disrupted hematopoiesis after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2013 Dec 27 [Epub ahead of print].
  • 67
    Yang L, Dybedal I, Bryder D et al. IFN-gamma negatively modulates self-renewal of repopulating human hemopoietic stem cells. J Immunol 2005;174:752757.
  • 68
    Murphy WJ, Welniak LA, Taub DD et al. Differential effects of the absence of interferon-gamma and IL-4 in acute graft-versus-host disease after allogeneic bone marrow transplantation in mice. J Clin Invest 1998;102:17421748.
  • 69
    Welniak LA, Blazar BR, Anver MR et al. Opposing roles of interferon-gamma on CD4+ T cell-mediated graft-versus-host disease: Effects of conditioning. Biol Blood Marrow Transplant 2000;6:604612.
  • 70
    Bryder D, Ramsfjell V, Dybedal I et al. Self-renewal of multipotent long-term repopulating hematopoietic stem cells is negatively regulated by Fas and tumor necrosis factor receptor activation. J Exp Med 2001;194:941952.
  • 71
    Dybedal I, Bryder D, Fossum A et al. Tumor necrosis factor (TNF)-mediated activation of the p55 TNF receptor negatively regulates maintenance of cycling reconstituting human hematopoietic stem cells. Blood 2001;98:17821791.
  • 72
    Pronk CJ, Veiby OP, Bryder D et al. Tumor necrosis factor restricts hematopoietic stem cell activity in mice: Involvement of two distinct receptors. J Exp Med 2011;208:15631570.
  • 73
    Beguin Y, Clemons GK, Oris R et al. Circulating erythropoietin levels after bone marrow transplantation: Inappropriate response to anemia in allogeneic transplants. Blood 1991;77:868873.
  • 74
    Cairo MS, Suen Y, Sender L et al. Circulating granulocyte colony-stimulating factor (G-CSF) levels after allogeneic and autologous bone marrow transplantation: Endogenous G-CSF production correlates with myeloid engraftment. Blood 1992;79:18691873.
  • 75
    Hamaguchi M, Yamada H, Morishima Y et al. Serum thrombopoietin level after allogeneic bone marrow transplantation: Possible correlations with platelet recovery, acute graft-versus-host disease and hepatic veno-occlusive disease. Nagoya Bone Marrow Transplantation Group. Int J Hematol 1996;64:241248.
  • 76
    Ishida A, Miyakawa Y, Tanosaki R et al. Circulating endogenous thrombopoietin, interleukin-3, interleukin-6 and interleukin-11 levels in patients undergoing allogeneic bone marrow transplantation. Int J Hematol 1996;65:6169.
  • 77
    Miller CB, Jones RJ, Zahurak ML et al. Impaired erythropoietin response to anemia after bone marrow transplantation. Blood 1992;80:26772682.
  • 78
    Uchiyama H, Shimazaki C, Fujita N et al. Kinetics of serum cytokines in adults undergoing peripheral blood progenitor cell transplantation. Br J Haematol 1994;88:639642.
  • 79
    Link H, Boogaerts MA, Fauser AA et al. A controlled trial of recombinant human erythropoietin after bone marrow transplantation. Blood 1994;84:33273335.
  • 80
    Calmettes C, Vigouroux S, Tabrizi R et al. Romiplostim (AMG531, Nplate) for secondary failure of platelet recovery after allo-SCT. Bone Marrow Transplant 2011;46:15871589.
  • 81
    Baron F, Storb R. Mesenchymal stromal cells: A new tool against graft-versus-host disease? Biol Blood Marrow Transplant 2012;18:822840.
  • 82
    Schneidawind D, Pierini A, Negrin RS. Regulatory T cells and natural killer T cells for modulation of GVHD following allogeneic hematopoietic cell transplantation. Blood 2013;122:31163121.
  • 83
    Bianco P, Cao X, Frenette PS et al. The meaning, the sense and the significance: Translating the science of mesenchymal stem cells into medicine. Nat Med 2013;19:3542.
  • 84
    Atanackovic D, Cao Y, Luetkens T et al. CD4+CD25+FOXP3+T regulatory cells reconstitute and accumulate in the bone marrow of patients with multiple myeloma following allogeneic stem cell transplantation. Haematologica 2008;93:423430.
  • 85
    Hartwell KA, Miller PG, Mukherjee S et al. Niche-based screening identifies small-molecule inhibitors of leukemia stem cells. Nat Chem Biol 2013;9:840848.
  • 86
    Ishikawa F, Yoshida S, Saito Y et al. Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region. Nat Biotechnol 2007;25:13151321.