17
Views
0
CrossRef citations to date
0
Altmetric
Review

Pathophysiology, prevention, and treatment of acute graft-versus-host disease

, &
Pages 31-44 | Published online: 07 Mar 2011

References

  • 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(12):945–956.
  • Cragg L, Blazar BR, Defor T, et al. A randomized trial comparing prednisone with antithymocyte globulin/prednisone as an initial systemic therapy for moderately severe acute graft-versus-host disease. Biol Blood Marrow Transplant. 2000;6(4A):441–447.
  • Storb R, Deeg HJ, Whitehead J, et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med. 1986;314(12):729–735.
  • Ratanatharathorn V Nash RA, Przepiorka D, et al. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood. 1998;92(7):2303–2314.
  • Weisdorf D, Hakke R, Blazar B, et al. Risk factors for acute graft-versus-host disease in histocompatible donor bone marrow transplantation. Transplantation. 1991;51(6):1197–1203.
  • Martin PJ, Schoch G, Fisher L, et al. A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. Blood. 1990;76(8):1464–1472.
  • Mielcarek M, Storb R. Graft-vs-host disease after non-myeloablative hematopoietic cell transplantation. Leuk Lymphoma. 2005;46(9): 1251–1260.
  • 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(7):1923–1930.
  • Bensinger W; Stem Cell Trialists’ Collaborative Group. Individual patient data meta-analysis of allogeneic peripheral blood stem cell transplant vs bone marrow transplant in the management of hematological malignancies: indirect assessment of the effect of day 11 methotrexate administration. Bone Marrow Transplant. 2006;38(8):539–546.
  • Blaise D, Kuentz M, Fortanier C, et al. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Societe Francaise de Greffe de Moelle. J Clin Oncol. 2000;18(3):537–546.
  • Couban S, Simpson DR, Barnett MJ, et al ; Canadian Bone Marrow Transplant Group. A randomized multicenter comparison of bone marrow and peripheral blood in recipients of matched sibling allogeneic transplants for myeloid malignancies. Blood. 2002;100(5):1525–1531.
  • Schmitz N, Beksac M, Hasenclever D, et al; European Group for Blood and Marrow Transplantation. Transplantation of mobilized peripheral blood cells to HLA-identical siblings with standard-risk leukemia. Blood. 2002;100(3):761–767.
  • Billingham RE. The biology of graft-versus-host reactions. Harvey Lect. 1966;62:21–78.
  • Prasad VK, Kernan NA, Heller G, O’Reilly RJ, Yang SY. DNA typing for HLA-A and HLA-B identifies disparities between patients and unrelated donors matched by HLA-A and HLA-B serology and HLA-DRB1. Blood. 1999;93(1):399–409.
  • Van Heeckeren WJ, Fanning LR, Meyerson HJ, et al. Influence of human leucocyte antigen disparity and graft lymphocytes on allogeneic engraftment and survival after umbilical cord blood transplant in adults. Br J Haematol. 2007;139(3):464–474.
  • Ferrara GB, Bacigalupo A, Lamparelli T, et al. Bone marrow transplantation from unrelated donors: the impact of mismatches with substitutions at position 116 of the human leukocyte antigen class I heavy chain. Blood. 2001;98(10):3150–3155.
  • Den Haan JM, Sherman NE, Blokland E, et al. Identification of a graft versus host disease-associated human minor histocompatibility antigen. Science. 1995;268(5216):1476–1480.
  • Gale RP, Bortin MM, van Bekkum DW, et al. Risk factors for acute graft-versus-host disease. Br J Haematol. 1987;67(4):397–406.
  • Hahn T, McCarthy PL Jr, Zhang MJ, et al. Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia. J Clin Oncol. 2008;26(35):5728–5734.
  • 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(5):281–285.
  • Ferrara JL, Reddy P. Pathophysiology of graft-versus-host disease. Semin Hematol. 2006;43(1):3–10.
  • Couriel DR, Saliba RM, Giralt S, et al. Acute and chronic graft-versus-host disease after ablative and nonmyeloablative conditioning for allogeneic hematopoietic transplantation. Biol Blood Marrow Transplant. 2004;10(3):178–185.
  • Mielcarek M, Martin PJ, Leisenring W, et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood. 2003;102(2):756–762.
  • Beatty PG, Clift RA, Mickelson EM, et al. Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med. 1985;313(13):765–771.
  • Kernan NA, Bartsch G, Ash RC, et al. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program. N Engl J Med. 1993;328(9):593–602.
  • Bross DS, Tutschka PJ, Farmer ER, et al. Predictive factors for acute graft-versus-host disease in patients transplanted with HLA-identical bone marrow. Blood. 1984;63(6):1265–1270.
  • Flowers ME, Pepe MS, Longton G, et al. Previous donor pregnancy as a risk factor for acute graft-versus-host disease in patients with aplastic anaemia treated by allogeneic marrow transplantation. Br J Haematol. 1990;74(4):492^96.
  • 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(7):1838–1845.
  • 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(5):663–668.
  • Seebach JD, Stussi G, Passweg JR, et al; GVHD Working Committee of Center for International Blood and Marrow Transplant Research. ABO blood group barrier in allogeneic bone marrow transplantation revisited. Biol Blood Marrow Transplant. 2005;11(12):1006–1013.
  • Clift RA, Buckner CD, Appelbaum FR, et al. Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens. Blood. 1990; 76(9):1867–1871.
  • Perez-Simon JA, Diez-Campelo M, Martino R, et al. Influence of the intensity of the conditioning regimen on the characteristics of acute and chronic graft-versus-host disease after allogeneic transplantation. Br J Haematol. 2005;130(3):394–403.
  • Aoudjhane M, Labopin M, Gorin NC, et al; Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT). Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT). Leukemia. 2005;19(12):2304–2312.
  • Uphoff DE. Perclusion of secondary phase of irradiation syndrome by inoculation of fetal hematopoietic tissue following lethal total-body x-irradiation. J Natl Cancer Inst. 1958;20(3):625–632.
  • Reisner Y, Itzicovitch L, Meshorer A, Sharon N. Hemopoietic stem cell transplantation using mouse bone marrow and spleen cells fractionated by lectins. Proc Natl Acad Sci U SA. 1978;75(6):2933–2936.
  • Dicke KA, Tridente G, van Bekkum DW. The selective elimination of immunologically competent cells from bone marrow and lymphocyte cell mixtures. 3. In vitro test for detection of immunocompetent cells in fractionated mouse spleen cell suspensions and primate bone marrow suspensions. Transplantation. 1969;8(4):422–434.
  • Rodt H, Kolb HJ, Netzel B, et al. GVHD suppression by incubation of bone marrow grafts with anti-T-cell globulin: effect in the canine model and application to clinical bone marrow transplantation. Transplant Proc. 1979;11(1):962–966.
  • Trentin JJ, Judd KP. Prevention of acute graft-versus-host (GVH) mortality with spleen-absorbed antithymocyte globulin (ATG). Transplant Proc. 1973;5(1):865–868.
  • Filipovich AH, McGlave P, Ramsay NK, Goldstein G, Kersey JH. Treatment of donor bone marrow with OKT3 (PAN-T monoclonal antibody) for prophylaxis of graft-vs-host disease (GvHD) in histocompatible allogeneic bone marrow transplantation (BMT): a pilot study. J Clin Immunol. 1982;2(3 Suppl):154S–157S.
  • Martin PJ, Hansen JA, Thomas ED. Preincubation of donor bone marrow cells with a combination of murine monoclonal anti-T-cell antibodies without complement does not prevent graft-versus-host disease after allogeneic marrow transplantation. J Clin Immunol. 1984;4(1):18–22.
  • Trigg ME, Billing R, Sondel PM, et al. Clinical trial depleting T lymphocytes from donor marrow for matched and mismatched allogeneic bone marrow transplants. Cancer Treat Rep. 1985; 69(4):377–386.
  • Herve P, Flesch M, Cahn JY, et al. Removal of marrow T cells with OKT3-OKT11 monoclonal antibodies and complement to prevent acute graft-versus-host disease. A pilot study in ten patients. Transplantation. 1985;39(2):138–143.
  • Marmont AM, Horowitz MM, Gale RP, et al. T-cell depletion of HLA-identical transplants in leukemia. Blood. 1991;78(8):2120–2130.
  • Wagner JE, Thompson JS, Carter SL, Kernan NA; Unrelated Donor Marrow Transplantation Trial. Effect of graft-versus-host disease prophylaxis on 3-year disease-free survival in recipients of unrelated donor bone marrow (T-cell Depletion Trial): a multi-centre, randomised phase II-III trial. Lancet. 2005;366(9487):733–741.
  • Bacigalupo A, Lamparelli T, Bruzzi P, et al. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood. 2001;98(10):2942–2947.
  • Finke J, Bethge WA, Schmoor C, et al; ATG-Fresenius Trial Group. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009;10(9):855–864.
  • Hale G, Bright S, Chumbley G, et al. Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement. Blood. 1983;62(4):873–882.
  • Chakraverty R, Peggs K, Chopra R, et al. Limiting transplantation-related mortality following unrelated donor stem cell transplantation by using a nonmyeloablative conditioning regimen. Blood. 2002;99(3):1071–1078.
  • Morris E, Thomson K, Craddock C, et al. Outcomes after alem-tuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. Blood. 2004;104(13):3865–3871.
  • Storb R, Epstein RB, Graham TC, Thomas ED. Methotrexate regimens for control of graft-versus-host disease in dogs with allogeneic marrow grafts. Transplantation. 1970;9(3):240–246.
  • Thomas ED, Buckner CD, Banaji M, et al. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood. 1977;49(4):511–533.
  • Deeg HJ, Storb R, Thomas ED, et al. Cyclosporine as prophylaxis for graft-versus-host disease: a randomized study in patients undergoing marrow transplantation for acute nonlymphoblastic leukemia. Blood. 1985;65(6):1325–1334.
  • Storb R, Deeg HJ, Thomas ED, et al. Marrow transplantation for chronic myelocytic leukemia: a controlled trial of cyclosporine versus methotrexate for prophylaxis of graft-versus-host disease. Blood. 1985;66(3):698–702.
  • Ringdén O, Backman L, Lönnqvist B, et al. A randomized trial comparing use of cyclosporin and methotrexate for graft-versus-host disease prophylaxis in bone marrow transplant recipients with haematological malignancies. Bone Marrow Transplant. 1986;1(1):41–51.
  • Deeg HJ, Lin D, Leisenring W, et al. Cyclosporine or cyclosporine plus methylprednisolone for prophylaxis of graft-versus-host disease: a prospective, randomized trial. Blood. 1997;89(10):3880–3887.
  • Kino T, Hatanaka H, Miyata S, et al. FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J Antibiot (Tokyo). 1987;40(9):1256–1265.
  • Przepiorka D, Ippoliti C, Khouri I, et al. Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after matched unrelated donor marrow transplantation. Blood. 1996; 88(11):4383–4389.
  • Nash RA, Etzioni R, Storb R, et al. Tacrolimus (FK506) alone or in combination with methotrexate or methylprednisolone for the prevention of acute graft-versus-host disease after marrow transplantation from HLA-matched siblings: a single-center study. Blood. 1995;85(12):3746–3753.
  • Nash RA, Antin JH, Karanes C, et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood. 2000;96(6):2062–2068.
  • Franklin TJ, Cook JM. The inhibition of nucleic acid synthesis by mycophenolic acid. Biochem J. 1969;113(3):515–524.
  • Suthanthiran M, Morris RE, Strom TB. Immunosuppressants: cellular and molecular mechanisms of action. Am J Kidney Dis. 1996;28(2):159–172.
  • Storb R, Yu C, Wagner JL, et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood. 1997;89(8):3048–3054.
  • Sabry W, Le Blanc R, Labbe AC, et al. Graft-versus-host disease prophylaxis with tacrolimus and mycophenolate mofetil in HLA-matched nonmyeloablative transplant recipients is associated with very low incidence of GVHD and nonrelapse mortality. Biol Blood Marrow Transplant. 2009;15(8):919–929.
  • Zohren F, Schroeder T, Czibere A, et al. Tacrolimus and mycofenolate mofetil as GvHD prophylaxis following nonmyeloablative conditioning and unrelated hematopoietic SCT for adult patients with advanced hematologic diseases. Bone Marrow Transplant. July 26, 2010. Epub ahead of print. DOI: 10.1038/bn2010.167.
  • Bolwell B, Sobecks R, Pohlman B, et al. A prospective randomized trial comparing cyclosporine and short course methotrexate with cyclosporine and mycophenolate mofetil for GVHD prophylaxis in myeloablative allogeneic bone marrow transplantation. Bone Marrow Transplant. 2004;34(7):621–625.
  • Piñana JL, Valcárcel D, Fernández-Avilés F, et al. MTX or mycophe-nolate mofetil with CsA as GVHD prophylaxis after reduced-intensity conditioning PBSCT from HLA-identical siblings. Bone Marrow Transplant. 2010;45(9):1449–1456.
  • Perkins J, Field T, Kim J, et al. A randomized phase II trial comparing tacrolimus and mycophenolate mofetil to tacrolimus and methotrexate for acute graft-versus-host disease prophylaxis. Biol Blood Marrow Transplant. 2010;16(7):937–947.
  • Storb R, Pepe M, Anasetti C, et al. What role for prednisone in prevention of acute graft-versus-host disease in patients undergoing marrow transplants? Blood. 1990;76(5):1037–1045.
  • Chao NJ, Schmidt GM, Niland JC, et al. Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prophylaxis of acute graft-versus-host disease. N Engl J Med. 1993;329(17):1225–1230.
  • Chao NJ, Snyder DS, Jain M, et al. Equivalence of 2 effective graft-versus-host disease prophylaxis regimens: results of a prospective double-blind randomized trial. Biol Blood Marrow Transplant. 2000;6(3):254–261.
  • Ruutu T, Volin L, Parkkali T, Juvonen E, Elonen E. Cyclosporine, methotrexate, and methylprednisolone compared with cyclosporine and methotrexate for the prevention of graft-versus-host disease in bone marrow transplantation from HLA-identical sibling donor: a prospective randomized study. Blood. 2000;96(7):2391–2398.
  • Griffith JP, Kim JL, Kim EE, et al. X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex. Cell. 1995;82(3):507–522.
  • Morice WG, Brunn GJ, Wiederrecht G, Siekierka JJ, Abraham RT. Rapamycin-induced inhibition of p34cdc2 kinase activation is associated with G1/S-phase growth arrest in T lymphocytes. J Biol Chem. 1993;268(5):3734–3738.
  • Altmeyer A, Dumont FJ. Rapamycin inhibits IL-1-mediated interferon-gamma production in the YAC-1 T cell lymphoma. Cytokine. 1993;5(2):133–143.
  • Lai JH, Tan TH. CD28 signaling causes a sustained down-regulation of I kappa B alpha which can be prevented by the immunosuppressant rapamycin. J Biol Chem. 1994;269(48):30077–30080.
  • Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood. 2005;105(12):4743–4748.
  • Antin JH, Kim HT, Cutler C, et al. Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation. Blood. 2003;102(5):1601–1605.
  • Alyea EP, Li S, Kim HT, et al. Sirolimus, tacrolimus, and low-dose methotrexate as graft-versus-host disease prophylaxis in related and unrelated donor reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2008;14(8):920–926.
  • Ho VT, Aldridge J, Kim HT, et al. Comparison of Tacrolimus and Sirolimus (Tac/Sir) versus Tacrolimus, Sirolimus, and minimethotrexate (Tac/Sir/MTX) as acute graft-versus-host disease prophylaxis after reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2009;15(7):844–850.
  • Rodriguez R, Nakamura R, Palmer JM, et al. A phase II pilot study of tacrolimus/sirolimus GVHD prophylaxis for sibling donor hematopoietic stem cell transplantation using 3 conditioning regimens. Blood. 2010;115(5):1098–1105.
  • Cutler C, Li S, Ho VT, et al. Extended follow-up of methotrexate-free immunosuppression using sirolimus and tacrolimus in related and unrelated donor peripheral blood stem cell transplantation. Blood. 2007;109(7):3108–3114.
  • Cutler C, Stevenson K, Kim HT, et al. Sirolimus is associated with veno-occlusive disease of the liver after myeloablative allogeneic stem cell transplantation. Blood. 2008;112(12):4425–4431.
  • Peritt D. Potential mechanisms of photopheresis in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2006;12 (1 Suppl 2):7–12.
  • Shaughnessy PJ, Bolwell BJ, van Besien K, et al. Extracorporeal photopheresis for the prevention of acute GVHD in patients undergoing standard myeloablative conditioning and allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2010;45(6):1068–1076.
  • Ruutu T, Eriksson B, Remes K, et al; Nordic Bone Marrow Transplantation Group. Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic stem cell transplantation. Blood. 2002;100(6):1977–1983.
  • Blazar BR, Weisdorf DJ, Defor T, et al. Phase 1/2 randomized, placebocontrol trial of palifermin to prevent graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Blood. 2006;108(9):3216–3222.
  • Van Lint MT, Uderzo C, Locasciulli A, 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(7):2288–2293.
  • Hings IM, Filipovich AH, Miller WJ, et al. Prednisone therapy for acute graft-versus-host disease: short-versus long-term treatment. A prospective randomized trial. Transplantation. 1993; 56(3): 577–580.
  • MacMillan ML, Weisdorf DJ, Wagner JE, et al. Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems. Biol Blood Marrow Transplant. 2002;8(7):387–394.
  • Lee SJ, Zahrieh D, Agura E, 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(5): 1559–1564.
  • Couriel DR, Saliba R, de Lima M, et al. A phase III study of infliximab and corticosteroids for the initial treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant. 2009;15(12):1555–1562.
  • Alousi AM, Weisdorf DJ, Logan BR, et al. Blood and Marrow Transplant Clinical Trials Network. Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network. Blood. 2009;114(3):511–517.
  • Uberti JP, Ayash L, Ratanatharathorn V 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(9):680–687.
  • Kim JG, Sohn SK, Kim DH, et al. Different efficacy of mycophenolate mofetil as salvage treatment for acute and chronic GVHD after allogeneic stem cell transplant. Eur J Haematol. 2004;73(1): 56–61.
  • Shaughnessy PJ, Bachier C, Grimley M, et al. Denileukin diftitox for the treatment of steroid-resistant acute graft-versus-host disease. Biol Blood Marrow Transplant. 2005;11(3):188–193.
  • Bolanos-Meade J, Jacobsohn DA, Margolis J, et al. Pentostatin in steroid-refractory acute graft-versus-host disease. J Clin Oncol. 2005; 23(12):2661–2668.
  • Van Lint MT, Milone G, Leotta 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(10):4177–4181.
  • Hsu B, May R, Carrum G, Krance R, Przepiorka D. Use of antithymocyte globulin for treatment of steroid-refractory acute graft-versus-host disease: an international practice survey. Bone Marrow Transplant. 2001;28(10):945–950.
  • Lopez M, Clarkson MR, Albin M, Sayegh MH, Najafian N. A novel mechanism of action for anti-thymocyte globulin: induction of CD4+CD25+Foxp3+ regulatory T cells. J Am Soc Nephrol. 2006; 17(10):2844–2853.
  • Arai S, Margolis J, Zahurak M, Anders V, Vogelsang GB. Poor outcome in steroid-refractory graft-versus-host disease with antithymocyte globulin treatment. Biol Blood Marrow Transplant. 2002;8(3):155–160.
  • MacMillan ML, Weisdorf DJ, Davies SM, et al. Early antithymocyte globulin therapy improves survival in patients with steroid-resistant acute graft-versus-host disease. Biol Blood Marrow Transplant. 2002;8(1):40–46.
  • Martin PJ, Schoch G, Fisher L, et al. A retrospective analysis of therapy for acute graft-versus-host disease: secondary treatment. Blood. 1991;77(8):1821–1828.
  • Przepiorka D, Phillips GL, Ratanatharathorn V et al. A phase II study of BTI-322, a monoclonal anti-CD2 antibody, for treatment of steroid-resistant acute graft-versus-host disease. Blood. 1998;92(11):4066–4071.
  • Knop S, Hebart H, Gratwohl A, et al. Treatment of steroid-resistant acute GVHD with OKT3 and high-dose steroids results in better disease control and lower incidence of infectious complications when compared to high-dose steroids alone: a randomized multicenter trial by the EBMT Chronic Leukemia Working Party. Leukemia. 2007;21(8):1830–1833.
  • Gleixner B, Kolb HJ, Holler E, et al. Treatment of aGVHD with OKT3: clinical outcome and side-effects associated with release of TNF alpha. Bone Marrow Transplant. 1991;8(2):93–98.
  • Carpenter PA, Lowder J, Johnston L, 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(6):465–471.
  • Byers VS, Henslee PJ, Kernan NA, et al. Use of an anti-pan T-lymphocyte ricin a chain immunotoxin in steroid-resistant acute graft-versus-host disease. Blood. 1990;75(7):1426–1432.
  • Willenbacher W, Basara N, Blau IW, Fauser AA, Kiehl MG. Treatment of steroid refractory acute and chronic graft-versus-host disease with daclizumab. Br J Haematol. 2001;112(3):820–823.
  • Anasetti C, Hansen JA, Waldmann TA, et al. Treatment of acute graft-versus-host disease with humanized anti-Tac: an antibody that binds to the interleukin-2 receptor. Blood. 1994;84(4):1320–1327.
  • Przepiorka D, Kernan NA, Ippoliti C, et al. Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. Blood. 2000;95(1):83–89.
  • Bay JO, Dhédin N, Goerner M, 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(6):782–788.
  • Massenkeil G, Rackwitz S, Genvresse I, Rosen O, Dörken B, Arnold R. Basiliximab is well tolerated and effective in the treatment of steroid-refractory acute graft-versus-host disease after allogeneic stem cell transplantation. Bone Marrow Transplant. 2002;30(12):899–903.
  • Funke VA, de Medeiros CR, Setubal DC, et al. Therapy for severe refractory acute graft-versus-host disease with basiliximab, a selective interleukin-2 receptor antagonist. Bone Marrow Transplant. 2006;37(10):961–965.
  • Martínez C, Solano C, Ferrá C, Sampol A, Valcárcel D, Pérez-Simón JA; Spanish Group for Stem Cell Transplantation (Grupo Español de Trasplante Hemopoyético y Terapia Celular). Alemtuzumab as treatment of steroid-refractory acute graft-versus-host disease: results of a phase II study. Biol Blood Marrow Transplant. 2009;15(5):639–642.
  • Macmillan ML, Couriel D, Weisdorf DJ, et al. A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease. Blood. 2007;109(6):2657–2662.
  • Busca A, Locatelli F, Marmont F, Ceretto C, Falda M. Recombinant human soluble tumor necrosis factor receptor fusion protein as treatment for steroid refractory graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2007;82(1):45–52.
  • Patriarca F, Sperotto A, Damiani D, et al. Infliximab treatment for steroid-refractory acute graft-versus-host disease. Haematologica. 2004;89(11):1352–1359.
  • Greinix HT, Volc-Platzer B, Kalhs P, et al. Extracorporeal photochemotherapy in the treatment of severe steroid-refractory acute graft-versus-host disease: a pilot study. Blood. 2000;96(7):2426–2431.
  • Greinix HT, Knobler RM, Worel N, et al. The effect of intensified extracorporeal photochemotherapy on long-term survival in patients with severe acute graft-versus-host disease. Haematologica. 2006;91(3):405–408.
  • Dall’Amico R, Messina C. Extracorporeal photochemotherapy for the treatment of graft-versus-host disease. Ther Apher. 2002; 6(4):296–304.
  • Le Blanc K, Frassoni F, Ball L, et al; Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008;371(9624): 1579–1586.
  • Von Bonin M, Kiani A, Platzbecker U, et al. Third-party mesenchymal stem cells as part of the management of graft-failure after haploidentical stem cell transplantation. Leuk Res. 2009; 33(12):e215–e217.
  • Kebriaei P, Isola L, Bahceci E, et al. Adult human mesenchymal stem cells added to corticosteroid therapy for the treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant. 2009;15(7):804–811.
  • Martin PJ, Uberti JP, Soiffer RJ, et al. Prochymal improves response rates in patients with steroid-refractory acute graft versus host disease (SR-GVHD) involving the liver and gut: results of a randomized, placebo-controlled, multicenter pPhase III trial in GVHD. Biol Blood Marrow Transplant: J Am Soc Blood Marrow Transplant. 2010;16(2):S169–S170.