Abstract
ALLOGENEIC bone marrow transplantation (BMT) has become the therapy of choice for the treatment of severe aplastic anaemia and severe combined immunodeficiency diseases and is considered beneficial for the treatment and possible cure of malignant diseases, especially lymphohaematopoietic malignancies1. Several serious complications, however, prevent the full realisation of the therapeutic potential of this procedure. To accept an allogeneic marrow graft, patients (even those treated for aplastic anaemia) have to be conditioned with cytoreductive agents like cyclophosphamide (Cy) or total body irradiation (TBI), agents that have relatively low therapeutic indices for immunosuppression and marked toxicities. Furthermore, patients, even if matched with their respective donors at the major histocompatibility complex (MHC), have after engrafting successfully, a high incidence of potentially fatal graft-versus-host disease (GvHD). Third, patients, who successfully engraft have a severe immunodeficiency for several months after transplantation that apparently contributes to potentially fatal opportunistic infections in the post-grafting period2. Attempts to overcome these complications have had only limited success. Cyclosporin A (Cs A), an undecapeptide of fungal origin3, has been reported to have very profound antilymphocytic activities with very low degrees of myelotoxicity4. It has been shown to suppress a variety of humoral and cellular immune phenomena5, including the rejection of renal allografts in rabbits.6 It seemed reasonable, therefore, to study its effects in an animal model of bone marrow transplantation. Cs A permits the full establishment of a rat marrow graft across the major histocompatibility barrier. Given post grafting it prevents GvHD in an AgB mismatched donor–recipient combination and allows recovery of T-dependent immune functions as early as 28 d after transplantation. Thus, Cs A seems to be a promising agent for use in clinical marrow transplantation.
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TUTSCHKA, P., BESCHORNER, W., ALLISON, A. et al. Use of cyclosporin A in allogeneic bone marrow transplantation in the rat. Nature 280, 148–151 (1979). https://doi.org/10.1038/280148a0
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DOI: https://doi.org/10.1038/280148a0
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