Abstract
First-line treatment of GVHD is based on steroids and produces sustained responses in 50–80% of patients with acute GVHD (aGVHD) and 40–50% of patients with chronic GVHD (cGVHD) depending on the initial disease severity. Non-responding children are offered second-line therapy with combinations of various agents, but currently available agents have not improved survival in these high-risk populations. In this minireview, we will focus on new agents to treat GVHD in paediatric patients.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Lorenz E, Uphoff D, Reid TR, Shelton E . Modification of irradiation injury in mice and guinea pigs by bone marrow injections. J Natl Cancer Inst 1951; 12: 197–201.
van Bekkum DW, de Vries MJ . The production of radiation chimaeras. Radiation Chimaeras. Logos Press Limited: London, UK, 1967, pp 20–78.
Billingham RE . The biology of graft-versus-host reactions. The Harvey Lectures 1966. Academic Press: New York, NY, 1966, pp 21–78.
Ferrara JLM, Deeg HJ . Graft-versus-host disease. N Engl J Med 1991; 325: 357–358.
Van Lint MT, Uderzo C, Locasciulli A, Majolino I, Scime R, Locatelli F et al. Early treatment of acute graft-versus-host disease with high- or low-dose 6-methylprednisolone: a multicenter randomized trial from the Italian Group for Bone Marrow Transplantation. Blood 1998; 92: 2288–2293.
Van Lint MT, Milone G, Leotta S, Uderzo C, Scimè R, Dallorso S et al. Treatment of acute graft-versus-host disease with prednisolone: significant survival advantage for day +5 responders and no advantage for nonresponders receiving anti-thymocyte globulin. Blood 2006; 107: 4177–4181.
Atkinson K . Chronic graft versus host disease. Bone Marrow Transplant 1990; 5: 69–82.
Sullivan KM, Witherspoon RP, Storb R, Deeg HJ, Dahlberg S, Sanders JE et al. Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-versus-host disease. Blood 1988; 72: 555–561.
Vogelsang GB . How I treat chronic graft versus host disease. Blood 2001; 97: 1196–1201.
Locatelli F, Uderzo C, Dini G, Zecca M, Arcese W, Messina C et al. Graft-versus-host disease in children: the AIEOP-BMT Group experience with cyclosporin A. Bone Marrow Transplant 1993; 12: 627–633.
Eisner MD, August CS . Impact of donor and recipient characteristics on the development of acute and chronic graft-versus-host disease following pediatric bone marrow transplantation. Bone Marrow Transplant 1995; 15: 663–668.
Kondo M, Kojima S, Horibe K, Kato K, Matsuyama T . Risk factors for chronic graft-versus-host disease after allogeneic stem cell transplantation in children. Bone Marrow Transplant 2001; 27: 727–730.
Atkinson K, Horowitz MM, Gale RP, van Bekkum DW, Gluckman E, Good RA et al. Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation. Blood 1990; 75: 2459–2464.
Ochs LA, Miller WJ, Filipovich AH, Haake RJ, McGlave PB, Blazar BR et al. Predictive factors for chronic graft-versus-host disease after histocompatible sibling donor bone marrow transplantation. Bone Marrow Transplant 1994; 13: 455–460.
Carlens S, Ringdén O, Remberger M, Lönnqvist B, Hägglund H, Klaesson S et al. Risk factors for chronic graft-versus-host disease after bone marrow transplantation: a retrospective single centre analysis. Bone Marrow Transplant 1998; 22: 755–761.
Zecca M, Prete A, Rondelli R, Lanino E, Balduzzi A, Messina C et al. Chronic graft versus host disease in children: incidence, risk factors, and impact on outcome. Blood 2002; 100: 1192–1200.
Lee SJ, Zahrieh D, Agura E, MacMillan ML, Maziarz RT, McCarthy Jr PL et al. Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial. Blood 2004; 104: 1559–1564.
Bordigoni P, Dimicoli S, Clement L, Baumann C, Salmon A, Witz F et al. Daclizumab, an efficient treatment for steroid-refractory acute graft-versus-host disease. Br J Haematol 2006; 135: 382–385.
Ho VT, Zahrieh D, Hochberg E, Micale E, Levin J, Reynolds C et al. Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Blood 2004; 104: 1226.
Bay JO, Dhédin N, Goerner M, Vannier JP, Marie-Cardine A, Stamatoullas A et al. Inolimomab in steroid-refractory acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: retrospective analysis and comparison with other interleukin-2 receptor antibodies. Transplantation 2005; 80: 782–788.
Funke VA, de Medeiros CR, Setúbal DC, Ruiz J, Bitencourt MA, Bonfim CM et al. Therapy for severe refractory acute graft-versus-host disease with basiliximab, a selective interleukin-2 receptor antagonist. Bone Marrow Transplant 2006; 37: 961–965.
Deeg HJ, Blazar BR, Bolwell BJ, Long GD, Schuening F, Cunningham J et al. Treatment of steroid-refractory acute graft-versus-host disease with anti-CD147 monoclonal antibody ABX-CBL. Blood 2001; 98: 2052–2058.
Couriel D, Saliba R, Hicks K, Ippoliti C, de Lima M, Hosing C et al. Tumor necrosis factor alpha blockade for the treatment of acute GVHD. Blood 2004; 104: 649–654.
Marty FM, Lee SJ, Fahey MM, Alyea EP, Soiffer RJ, Antin JH et al. Infliximab use in patients with severe graft-versus-host disease and other emerging risk factors of non-Candida invasive fungal infections in allogeneic hematopoietic stem cell transplant recipients. A cohort study. Blood 2003; 102: 2768–2776.
Uberti JP, Ayash L, Ratanatharathorn V, Silver S, Reynolds C, Becker M et al. Pilot trial on the use of etanercept and methylprednisolone as primary treatment for acute graft-versus-host disease. Biol Blood Marrow Transplant 2005; 11: 680–687.
Carpenter PA, Lwder J, Johnston L, Frangoul H, Khoury H, Parker P et al. A phase II multicenter study of visilizumab, humanized anti-CD3 antibody, to treat steroid refractory acute graft versus host disease. Biol Blood Marrow Transplant 2005; 11: 465–471.
Toor AA, Stiff PJ, Nickoloff BJ, Rodriguez T, Klein JL, Gordon KB . Alefacept in corticosteroid refractory graft versus host disease: early results indicate promising activity. J Dermatol Treat 2007; 18: 13–18.
Aggarwal S, Pittinger F . Human mesenchymal stem cell modulate allogeneic immune cell responses. Blood 2005; 105: 1815–1822.
Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC . Suppression of allogeneic T cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 2003; 75: 389–397.
Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 2002; 30: 42–48.
Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 99: 3838–3843.
Le Blanc K, Ringdén O . Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11: 321–334.
Sundin M, Orvell C, Rasmusson I, Sundberg B, Ringdén O, Le Blanc K . Mesenchymal stem cells are susceptible to human herpes viruses, but do not harbor these viruses in the healthy seropositive individual. Bio Bone Marrow Transplant 2006; 37: 1051–1059.
Müller I, Kordowich S, Holzwarth C, Isensee G, Lang P, Neunhoeffer F et al. Application of multipotent mesenchymal stromal cells in pediatric patients following allogeneic stem cell transplantation. Blood Cells Mol Dis 2008; 40: 25–32.
Vianello F, Dazzi F . Mesenchymal stem cells for graft-versus-host disease: a double edged sword? Leukemia 2008; 22: 463–465.
Ning H, Yang F, Jiang M, Hu L, Feng K, Zhang J et al. The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematological malignancy patients: outcome of a pilot clinical study. Leukemia 2008; 22: 593–599.
Couriel DR, Hosing C, Saliba R, Shpall EJ, Anderlini P, Rhodes B et al. Extracorporeal photochemotherapy for the treatment of steroid-resistant chronic GVHD. Blood 2006; 107: 3074–3080.
Couriel D, Hosing C, Saliba R, Shpall EJ, Andelini P, Popat U et al. Extracorporeal photopheresis for acute and chronic graft-versus-host disease: does it work? Biol Blood Marrow Transplant 2006; 12: 37–40.
Foss FM, Gorgun G, Miller KB . Extracorporeal photopheresis in chronic graft-versus-host disease. Bone Marrow Transplant 2002; 29: 719–725.
Gorgun G, Miller KB, Foss FM . Immunologic mechanisms of extracorporeal photochemotherapy in chronic graft-versus-host disease. Blood 2002; 100: 941–947.
Di Renzo M, Sbano P, De Aloe G, Pasqui AL, Rubegni P, Ghezzi A et al. Extracorporeal photopheresis affects co-stimulatory molecule expression and interleukin-10 production by dendritic cells in graft-versus-host disease patients. Clin Exp Immunol 2008; 151: 407–413.
Berger M, Pessolano R, Albiani R, Asaftei S, Barat V, Carraro F et al. Extracorporeal photopheresis for steroid resistant graft versus host disease in pediatric patients: a pilot single institution report. J Pediatr Hematol Oncol 2007; 29: 678–687.
Svegliati S, Olivieri A, Campelli N, Luchetti M, Poloni A, Trappolini S et al. Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood 2007; 110: 237–241.
Bonner JC . Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth Factor Rev 2004; 15: 255–273.
Majbail NS, Schiffer CA, Weisdorf DJ . Improvement of pulmonary function with imatinib mesylate in bronchiolitis obliterans following allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2006; 12: 789–791.
Zaja F, Bacigalupo A, Patriarca F, Stanzani M, Van Lint MT, Filì C et al. Treatment of refractory chronic GVHD with rituximab: a GITMO study. Bone Marrow Transplant 2007; 40: 273–277.
Cutler C, Miklos D, Kim HT, Treister N, Woo SB, Bienfang D et al. Rituximab for steroid-refractory chronic graft-versus-host disease. Blood 2006; 108: 756–762.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Berger, M., Biasin, E., Saglio, F. et al. Innovative approaches to treat steroid-resistant or steroid refractory GVHD. Bone Marrow Transplant 42 (Suppl 2), S101–S105 (2008). https://doi.org/10.1038/bmt.2008.294
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2008.294