Abstract
We have previously reported that the elimination of T-lymphocytes (>99%) from the donor bone marrow prevents significant graft versus host disease (GvHD). This has been confirmed by other centres. Many of these groups have applied monoclonal antibodies with cytolytic rabbit complement. In some of these studies mostly patients with fully matched sibling donors have been studied and no further immunosuppression has been given during the regeneration period. The experience here shows that the haemopoietic regeneration (to recover a total leucocyte count of 1.0 × 109/l) has only been minimally delayed (mean 25 days) when compared to patients receiving standard methotrexate (Mtx) GvHD prophylaxis (22 days). The incidence of cylomegalovirus (CMV) infections (14%; none fatal) was lower than that in our previous 54 patients (43% CMV infections, 13% fatal). Furthermore, no fatal pneumonitis was seen. The regeneration of T-cells in our patients has shown normal values of T8-positive cells in the circulation from 45 to 50 days onwards, as opposed to the previous groups of patients whose T8-positive cells regenerated to 3–4 times higher than normal values. These observations indicate that T-cell depletion with monoclonal antibodies is an effective method for preventing GvHD, but further studies are necessary to investigate the cause(s) of a new occasional complication, the rejection of the newly established bone marrow.
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Thomas E D, Fefer A, Buckner C D, Storb R: Current status of bone marrow transplantation for aplastic anaemia and leukaemia.Blood 49, 671–681 (1972).
Merion R M, White D J G, Thiru S, Evans D B, Calne R Y: Cyclosporine: five years' experience in cadaveric renal transplantation.New Engl J Med 30, 148 (1984).
Speck B, Bortin M M, Champlin R, Goldman J M, Herzig R H, McGlave P B, Messner H A, Weiner R S, Rimm A A: Allogeneic bone marrow transplantation for chronic myelogenous leukaemia.Lancet i, 665–668 (1984).
Fefer A, Cheever M A, Greenberg P D, Appelbaum F R, Boyd C N, Buckner C D, Kaplan H G, Ramberg R, Sandbers J E, Storb R, Thomas E D: Treatment of chronic granulocytic leukemia with chemoradiotherapy and transplantation of marrow from identical twins.New Engl J Med 306, 63–69 (1982).
Rodt H, Thierfelder S, Eulitz M: Antilymphocyte antibodies and marrow transplantation. III. Effect of heterologous anti-brain antibodies on acute secondary disease in mice.Eur J Immunol 4, 25–29 (1974).
Korbling M, Fliedner T M, Calvo Wet al: Albumin density gradient purification of canine hemopoietic blood cells (HBSC): long-term allogeneic engraftment without GvH-reaction.Exp Haematol 7, 277–288 (1979).
Wagemaker G, Vriesendorp H M, Van Bekkum D W: Successful bone marrow transplantation across major histocompatibility barriers in rhesus monkeys.Transplant Proc 13, 875–880 (1981).
Sprent J, Korngold R: Immunogenetics of graftversus-host reactions to minor histocompatibility antigens.Immunol Today 2, 189–195 (1981).
Granger S M, Janossy G, Francis G, Blacklock H, Poulter L W, Hoffbrand A V: Elimination of T lymphocytes from human bone marrow with monoclonal anti-T antibodies and cytolytic complement.Br J Haemat 50, 367–374 (1982).
Herve P, Flesch M, Cahn J Y, Radacot E, Pouvier E, Lamy B, Rozenbaum A, Noir A, Leconte des floris OKT3-OKT11 antibodies and complement to prevent acute graft versus host disease (in press).
Prentice H G, Blacklock H A, Janossy G, Bradstock K F, Skeggs D, Goldstein G, Hoffbrand A V: Use of the anti-T monoclonal antibody OKT3 for prevention of acute graft versus host disease (GvHD) in allogeneic bone marrow transplantation for acute leukaemia.Lancet i, 700–703 (1982).
Martin P, Hansen J, Storb R, Thomas E D: The use of monoclonal antibody cocktails for preventing GvHD, in: Larizza P (eds) (in press).
Mugishima H, Terasaki P I, Sueyoshi A, Billing R: Human complement in treatment of bone marrow cells with monoclonal antibody.Lancet ii, 1194–1195 (1983).
Hale G, Bright S, Chumbley G, Hoang T, Metcalf D, Munro A, Waldmann H: Removal of T-cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement.Blood 62, 873–882 (1984).
Bodger M, Francis G E, Delia D, Thomas J A, Granger S M, Janossy A: A monoclonal antibody specific for immature human haemopoietic cells and T lineage cells.J Immun 127, 2269–2274 (1981).
Tindle R W, Catovsky D, Griffin J, Janossy G, Campana D, Chan L: A novel anti-myeloid antibody 3C5 recognizes early precursors (in press).
Bauman J G J, Mulder D H, van den Engh G J: The effects of surface antigen labelling on spleen colony formation.Eur J Immun 14 (in press).
Martin P J, Hansen J A, Thomas E D: Use of microfluorometry in bone marrow transplantation (in press).
Ivory K, Janossy G, Kluin-Nelemans H: (in preparation).
Gilmore M J M L, Prentice H G, Blacklock H A, Ma D D F, Janossy G, Hoffbrand A V: A technique for rapid isolation of bone marrow mononuclear cells using ficoll-metrizoate and the IBM 2991 blood cell processor.Br J Haemat 50, 619–626 (1982).
Favrot M, Janossy G, Tidman N, Blacklock H A, Lopez E, Bofill M, Lampert I, Morgenstern G, Powles Ret al: T-cell regeneration after allogeneic bone marrow transplantation.Clin Exp Immun 54, 59–72 (1983).
Vines R L, Coleman M S, Hutton J J: Reappearance of terminal deoxynucleotidyl transferase containing cells in rat bone marrow following corticosteroid administration.Blood 56, 501–509 (1980).
Witherspoon R P, Storb R, Ochs H D, Fluoronoy N, Kopecky K J, Sullivan K M, Deeg H J, Sosa R, Noel D R, Atkinson K, Thomas E D: Recovery of antibody production in human allogeneic marrow graft recipients: influence of time posttransplantation, presence or absence of chronic GvHD and anti-lymphocyte globulin treatment.Blood 58, 360–368 (1981).
Steinmann G G: Changes of the human thymus during aging, in: Muller-Hermelink H K (ed):The Thymus: histophysiology and pathology. Current Topics in Pathology. Berlin, Springer (1984).
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Janossy, G., Prentice, H.G., Hoffbrand, A.V. et al. The role of monoclonal antibodies in the prevention of graft versus host disease. Med. Oncol. & Tumor Pharmacother. 1, 279–284 (1984). https://doi.org/10.1007/BF02934536
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DOI: https://doi.org/10.1007/BF02934536