Summary:
We retrospectively evaluated response to monoclonal antibody directed against CD3 (OKT3) treatment in 43 patients with steroid-resistant acute graft-versus-host disease (aGvHD) following allogeneic hematopoietic cell transplantation. Median duration of OKT3 therapy was 9 (range, 1–20) days. In all, 20 cycles were administered as second-line and 28 as third-plus line treatment. Side effects were mild to moderate. Overall response rate was 69 with 12% complete remissions and best response in skin involvement. Proportional reduction of concomitant steroids was higher in responding patients. Five patients (12%) achieved durable responses. Pharmacokinetic studies of OKT3 showed adequate plasma levels (⩾1000 ng/ml) in 13 of 17 evaluable patients after a median of 6 (1–11) days on treatment. OKT3 became undetectable shortly after discontinuation of therapy. Median survival for all patients was 80 (2 to 2474+) days. There was a trend for better survival for patients on second-line vs third-plus line treatment (146 vs 46 days; P=0.07) and significant longer survival for patients with grade II when compared to those with grade III/IV aGvHD (206 vs 47 days; P=0.039). We conclude that salvage treatment with OKT3 shows considerable efficiency, however, sometimes of transient nature, and is well tolerated in patients with corticosteroid-resistant aGvHD.
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References
McCaul KG, Nevill TJ, Barnett MJ et al. Treatment of steroid-resistant acute graft-versus-host disease with rabbit antithymocyte globulin. J Hematother Stem Cell Res 2000; 9: 367–374.
Hansen JA, Gooley TA, Martin PJ et al. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med 1998; 338: 962–968.
Remberger M, Aschan J, Barkholt L et al. Treatment of severe acute graft-versus-host disease with anti-thymocyte globulin. Clin Transplant 2001; 15: 147–153.
Ruutu T, Hermans J, van Biezen A et al. How should corticosteroids be used in the treatment of acute GVHD? EBMT Chronic Leukemia Working Party. European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 1998; 22: 614–615.
Herbelin C, Stephan JL, Donadieu J et al. Treatment of steroid-resistant acute graft-versus-host disease with an anti-IL-2-receptor monoclonal antibody (BT 563) in children who received T cell-depleted, partially matched, related bone marrow transplants. Bone Marrow Transplant 1994; 13: 563–569.
Tse JC, Moore TB . Monoclonal antibodies in the treatment of steroid-resistant acute graft-versus-host disease. Pharmacotherapy 1998; 18: 988–1000.
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: 4066–4071.
Buysmann S, Bemelman FJ, Schellekens PT et al. Activation and increased expression of adhesion molecules on peripheral blood lymphocytes is a mechanism for the immediate lymphocytopenia after administration of OKT3. Blood 1996; 87: 404–411.
Glucksberg H . A randomized clinical trial of OKT3 monoclonal antibody for acute rejection of cadaveric renal transplants. Ortho Multicenter Transplant Study Group. N Engl J Med 1985; 313: 337–342.
Glucksberg H, Storb R, Fefer A et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.
Martin PJ, Schoch G, Fisher L et al. A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. Blood 1990; 76: 1464–1472.
Goldstein G, Fuccello AJ, Norman DJ et al. OKT3 monoclonal antibody plasma levels during therapy and the subsequent development of host antibodies to OKT3. Transplantation 1986; 42: 507–511.
Bach JF, Chatenoud L . Immunologic monitoring of Orthoclone OKT3-treated patients: the problem of antimonoclonal immune response. Transplant Proc 1987; 19 (Suppl. 1): 17–20.
Jeyarajah DR, Thistlethwaite Jr JR . General aspects of cytokine-release syndrome: timing and incidence of symptoms. Transplant Proc 1993; 25 (Suppl. 1): 16–20.
Ruutu T, Niederwieser D, Gratwohl A, Apperley JF . A survey of the prophylaxis and treatment of acute GVHD in Europe: a report of the European Group for Blood and Marrow, Transplantation (EBMT). Chronic Leukaemia Working Party of the EBMT. Bone Marrow Transplant 1997; 19: 759–764.
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: 2288–2293.
Racadot E, Milpied N, Bordigoni P et al. Sequential use of three monoclonal antibodies in corticosteroid-resistant acute GVHD: a multicentric pilot study including 15 patients. Bone Marrow Transplant 1995; 15: 669–677.
Deeg HJ, Loughran Jr TP, Storb R et al. Treatment of human acute graft-versus-host disease with antithymocyte globulin and cyclosporine with or without methylprednisolone. Transplantation 1985; 40: 162–166.
Gluckman E, Devergie A, Varin F et al. Treatment of steroid resistant severe acute graft-versus host disease with a monoclonal pan T OKT3 antibody. Exp Hematol 1984; 12 (Suppl. 15): 66–67.
Gratama JW, Jansen J, Lipovich RA et al. Treatment of acute graft-versus-host disease with monoclonal antibody OKT3. Clinical results and effects on circulating T lymphocytes. Transplantation 1984; 38: 469–474.
Hebart H, Ehninger G, Schmidt H et al. Treatment of steroid-resistant graft-versus-host disease after allogeneic bone marrow transplantation with anti-CD3/TCR monoclonal antibodies. Bone Marrow Transplant 1995; 15: 891–894.
Todd PA, Brogden RN . Muromonab CD3. A review of its pharmacology and therapeutic potential. Drugs 1989; 37: 871–899.
Conlon Jr J, Carmody M, Donohoe J et al. Cytomegalovirus infection as a complication of OKT3 therapy in kidney transplant recipients. Ir J Med Sci 1992; 161: 630–632.
Swinnen LJ . Transplantation-related lymphoproliferative disorder: a model for human immunodeficiency virus-related lymphomas. Semin Oncol 2000; 27: 402–408.
Carpenter PA, Appelbaum FR, Corey L et al. A humanized non-FcR-binding anti-CD3 antibody, visilizumab, for treatment of steroid-refractory acute graft-versus-host disease. Blood 2002; 99: 2712–2719.
Birkeland SA, Hamilton-Dutoit S . Is posttransplant lymphoproliferative disorder (PTLD) caused by any specific immunosuppressive drug or by the transplantation per se? Transplantation 2003; 76: 984–988.
Chatenoud L . Immunologic monitoring during OKT3 therapy. Clin Transplant 1993; 7: 422–430.
Waller EK, Langston AA, Lonial S et al. Pharmacokinetics and pharmacodynamics of anti-thymocyte globulin in recipients of partially HLA-matched blood hematopoietic progenitor cell transplantation Biol. Blood Marrow Transplant 2003; 9: 460–471.
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Knop, S., Hebart, H., Gscheidle, H. et al. OKT3 muromonab as second-line and subsequent treatment in recipients of stem cell allografts with steroid-resistant acute graft-versus-host disease. Bone Marrow Transplant 36, 831–837 (2005). https://doi.org/10.1038/sj.bmt.1705132
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DOI: https://doi.org/10.1038/sj.bmt.1705132
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