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Initial treatment of acute graft-versus-host disease with a murine monoclonal antibody directed to the human α/β T cell receptor

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A murine IgG2b monoclonal antibody directed to the constant part of the human α/β T cell receptor (BMA031) was investigated in a pilot study as an initial treatment for acute graft-versus-host disease (aGvHD) after allogeneic bone marrow transplantation. The treatment protocol consisted of 5 mg BMA031 on 5 consecutive days with continuation of the prophylactic baseline immuno suppression using cyclosporin. Seven patients with grades II–III acute graft-versus-host disease were entered on the protocol and six patients completed the full treatment course. Mild to moderate acute adverse reactions to the first BMA031 infusion occurred in three patients. A nearly complete decline of circulating T lymphocytes was observed during BMA031 therapy, but the T cells returned to pretreatment values within 1 week after the last infusion. Serum pharmacokinetics of free antibody best fitted to a two-compartment open model with a mean initial half-life of 6 h and an estimated mean terminal half-life of 40 h. One patient developed antimurine antibodies of the IgM subclass. In five patients a complete and sustained resolution of all disease manifestations was attained, while in one patient a temporary response of skin involvement with aGvHD was noted. These results indicate that BMA031 can be safely administered as initial treatment of aGvHD. The therapeutic responses observed warrant its further clinical evaluation in this setting.

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  1. 1.

    Beelen DW, Graeven U, Ryschka U, Quabeck K, Grosse-Wilde H, Keweloh H-Ch, Kölbel M, Schaefer UW (1989) Primary treatment and prophylaxis of acute graft versus host disease with a combination of a monoclonal antibody against the human α/β-T-cell-receptor and ciclosporin (abstract 220) Blut 299

  2. 2.

    Beelen DW, Quabeck K, Kaiser B, Wiefelspütz J, Scheulen ME, Graeven U, Grosse-Wilde H, Sayer HG, Schaefer UW (1990) Six weeks of continuous intravenous cyclosporine and short-course methotrexate as prophylaxis for acute graft-versus-host disease after allogeneic bone marrow transplantation. Transplantation 50: 421

  3. 3.

    Byers VS, Henslee PJ, Kernan NA, Blazar BR, Gingrich R, Philips GL, LeMaistre CF, Gilliland G, Antin JH, Martin P, Tutschka PJ, Trown P, Ackerman SK, O'Reilly RJ, Scannon PJ (1990) Use of an anti-pan T-lymphocyte ricin A chain immunotoxin in steroid-resistant acute graft-versus-host disease. Blood 75: 1426

  4. 4.

    Deeg HJ, Storb R (1986) Acute and chronic graft-versus-host disease: clinical manifestations, prophylaxis and treatment. J Natl Cancer Inst 76: 1325

  5. 5.

    Gale RP, Bortin MM, Van Bekkum DW, Biggs JC, Dicke KA, Gluckman E, Good RA, Hoffmann RG, Kay HEM, Kersey JH, Marmont A, Massoka T, Rimm AA, van Rood JJ, Zwaan FE (1987) Risk factors for acute graft-versus-host disease. Br J Haemtol 67: 397

  6. 6.

    Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, Lerner KG, Thomas ED (1974) Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation 18: 295

  7. 7.

    Gratama JW, Jansen J, Lipovich A, Tanke HJ, Goldstein G, Zwaan FE (1984) Treatment of acute graft-versus-host disease with monoclonal antibody OKT3. Transplantation 38: 469

  8. 8.

    Hervé P, Wijdenes J, Bergerat JP, Milpied N, Gaud C, Bordigoni P (1988) Treatment of acute graft-versus-host disease with monoclonal antibody to IL-2-receptor. Lancet ii: 1072

  9. 10.

    Karnofsky DA, Abelman WH, Craver LF, Burchenal JH (1948) The use of the nitrogen mustards in the palliative treatment of carcinoma. Cancer 1: 634

  10. 11.

    Kennedy MS, Deeg HJ, Storb R, Doney K, Sullivan KM, Witherspoon RP, Appelbaum FR, Stewart P, Sanders J, Buckner CD, Martin P, Weiden P, Thomas ED (1985) Treatment of acute graft-versushost disease after allogeneic marrow transplantation. N Engl J Med 78: 978

  11. 12.

    Kurrle R, Seyfert W, Trautwein A, Seiler FR (1985) Cellular mechanisms of T cell activation by modulation of the T3 antigen complex. Transplant Proc 17: 880

  12. 13.

    Martin PJ, Hansen JA, Anasetti C, Zutter M, Durname D, Storb R, Thomas ED (1988) Treatment of acute graft-versus-host disease with anti-CD3 monoclonal antibodies. Am J Kidney Dis 3: 149

  13. 14.

    Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47: 207

  14. 15.

    Remlinger K, Martin PJ, Hansen JA, Doney KC, Smith A, Deeg HJ, Sullivan K, Storb R, Thomas ED (1985) Murine monoclonal anti-T-cell antibodies for treatment of steroid-resistant acute graft-versushost disease. Hum Immunol 9: 21

  15. 16.

    Thomas ED, Storb R, Clift RA, Fever A, Johnson FL, Neiman PE, Lerner KG, Glucksberg H, Buckner CD (1975) Bone marrow transplantation. N Engl J Med 292: 895

  16. 17.

    Vogelsang GB, Hess AD, Santos GW (1988) Acute graft-versus-host disease: clinical characteristics in the cyclosporine era. Medicine 67: 163

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Correspondence to Dietrich W. Beelen.

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Beelen, D.W., Grosse-Wilde, H., Ryschka, U. et al. Initial treatment of acute graft-versus-host disease with a murine monoclonal antibody directed to the human α/β T cell receptor. Cancer Immunol Immunother 34, 97–102 (1991).

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Key words

  • Bone marrow transplantation
  • Acute graft-versus-host disease
  • Monoclonal antibody