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Alternatives to donor matching for control of graft-versus-host disease

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Abstract

Graft-versus-host disease (GvHD) after bone-marrow transplantation in dogs is controlled by many different genetic systems. In littermate combinations identical for the major histocompatibility complex (MHC) the number of systems that influence GvHD is related to the number of donor lymphocytes injected. If the number of donor lymphocytes administered is sufficiently low, minor histocompatibility systems do not influence survival after bone-marrow transplantation. With increasing numbers of donor lymphocytes the beneficial influence of MHC matching on GvH incidence and severity disappears and minor histocompatibility antigens, coded for on at least two other autosomal chromosomes as well as possibly the Y chromosome, can cause severe GvHD. In contrast, the X chromosome does not appear to carry a histocompatibility system that is of relevance to GvHD control. The severity and tissue distribution of histological signs of GvHD in recipients of bone-marrow and lymph-node cells from MHC-identical donors are similar to those in recipients of MHC-mismatched bone-marrow cells. Female donors do appear to cause severe GvHD more frequently than males. In contrast to rhesus monkey and human bone-marrow cells, dog bone-marrow cells are negative in PHA tests. This is in accordance with the generally benign course of GvHD in dogs that are treated with bone-marrow cells only from histocompatible littermate donors. The influence of the sex of the bone-marrow donor on GvHD incidence and severity is not reflected in differences between PHA tests with male and female dog lymphocytes. A better predictive test for GvH potential than the PHA test appears to be needed. Alternatives to additional donor selection for the prevention of GvHD in histocompatible recipients appear to be the use of a male donor and the removal of lymphocytes from bone-marrow-cell suspensions prior to transplantation.

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References

  • Advisory Committee of the International Bone Marrow Transplant Registry: Severe combined immunodeficiency disease. Characterization of the disease and results of transplantation. JAMA 238: 591–600, 1977

    Google Scholar 

  • Advisory Committee of the International Bone Marrow Transplant Registry: Treatment of 144 patients with severe aplastic anemia using immunosuppression and allogeneic bone marrow transplantation. Transplant Proc. 13: 227, 1981

    Google Scholar 

  • Bukhart, P. T. and Meeuwiszen, H. J.: Immunocompetent cells in human and primate marrow. Transplantation 16: 372–373, 1973

    Google Scholar 

  • Claman, H. N.: Bone marrow T cells. I. Response to the T cell mitogens, phytohemagglutinin and Concanavalin A. J. Immunol. 112: 960–964, 1974

    Google Scholar 

  • Dicke, K. A., Tridente, G., and van Bekkum, D. W.: The selective elimination of immunologically competent cells from bone marrow and lymphocyte cell mixtures. Transplantation 8: 422–428, 1969

    Google Scholar 

  • Dicke, K. A. and van Bekkum, D. W.: Allogeneic bone marrow transplantation after elimination of immunocompetent cells by means of density gradient centrifugation. Transplant. Proc. 3: 366–370, 1971

    Google Scholar 

  • Dicke, K. A., Löwenberg, B., and Nieuwerkerk, H. T. M.: Elimination of lymphocytes from human marrow suspensions: gradient versus small marrow aspirates. Transplant. Proc. 7 (suppl. 1): 863–866, 1975

    Google Scholar 

  • Elkins, W. L. and Palm, J.: Identification of a single strong histocompatibility locus in the rat by normal spleen cell transfer. Ann. N. Y. Acad. Sci. 129: 573–576, 1966

    Google Scholar 

  • Epstein, R. B., Bryant, J., and Thomas, E. D.: Cytogenetic demonstration of permanent tolerance in adult outbred dogs. Transplantation 5: 267–272, 1967

    Google Scholar 

  • Ford, C. E.: Traffic of lymphoid cells in the body. In G. E. W. Wolstenhome, and R. Porter (eds.): The Thymus: Experimental and Clinical Studies, pp. 131–152, Little, Brown and Co., Boston, 1966

    Google Scholar 

  • Halle-Pannenko, O., Pritchard, L. L., Motta, R., and Mathe, G.: Non H-2 antigens can induce high GvH mortality in adult recipients of normal spleen cells. Biomedicine 28: 253–255, 1978

    Google Scholar 

  • Jaffe, W. P. and Payne, L. N.: The genetic basis for the graft against host reaction between inbred lines of fowls. Differences between the rease heath C and I inbred lines. Immunology 5: 399–406, 1962

    Google Scholar 

  • Joint Report of the 2nd International Workshop on Canine Immunogenetics. Transplant. Proc. 8: 289–314, 1976

    Google Scholar 

  • Kolb, H., Sale, G. E., Lerner, K. G., Storb, R., and Thomas, E. D.: Pathology of acute graft-versus-host disease in the dog. Am. J. Pathol. 96: 581–594, 1979

    Google Scholar 

  • Korngold, R. and Sprent, J.: Lethal graft-versus-host disease after bone marrow transplantation across minor histocompatibility barriers in mice. Prevention by removing mature T cells from marrow. J. Exp. Med. 148: 1678–1698, 1978

    Google Scholar 

  • Nelson, B., Calvo, W., Fliedner, T. M., Herbst, E., Bruch, C., Schnappauf, H. P., and Flad, H. D.: The repopulation of lymph nodes of dogs after 1200 R whole body X-irradiation and intravenous administration of mononclear blood leukocytes. Am. J. Pathol. 84: 259–282, 1976

    Google Scholar 

  • Meera Khan, P., Los, W. R. T., van der Does, J. A., and Epstein, R. B.: Isoenzyme markers in dog blood cells. Transplantation 15: 624–628, 1973

    Google Scholar 

  • Rodt, H., Kolb, H. J., Netzel., B., Rieder, I., Janka, G., Belohradsky, B., Haas, R. J., and Thierfelder, S.: 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. 11: 962–966, 1979

    Google Scholar 

  • Selden, J. R. and Wachtel, S. S.: H-Y antigen in the dog. Transplantation 24: 289–289, 1977

    Google Scholar 

  • Simonson, M.: Immunogenetic speculations on human kidney transplants. Transplantation 4: 354–364, 1966

    Google Scholar 

  • Storb, R., Rudolph, R. H., Kolb, H. J., Graham, T. C., Mickelson, E., Erickson, V., Lerner, K. G., Kolb, H., and Thomas, E. D.: Marrow grafts between DLA matched canine littermates. Transplantation 15: 92–100, 1973

    Google Scholar 

  • Storb, R., Thomas, E. D., Buckner, C. D., Clift, R. A., Johnson, F. L., Fefer, A., Glucksberg, H., Giblett, E. R., Lerner, K. G., and Neiman, P.: Allogeneic marrow grafting for treatment of aplastic anemia. Blood 43: 157–180, 1974

    Google Scholar 

  • Storb, R., Prentice, P. L., and Thomas, E. D.: Treatment of aplastic anemia by marrow transplantation from HLA identical siblings. Prognostic factors associated with graft versus host disease and survival. J. Clin. Invest. 59: 625–632, 1977

    Google Scholar 

  • Tartakovsky, B., Sega, S., Shani, A., Hellerstein, S., Weinstein, Y., and Bentwich, Z.: Segregation of human peripheral blood lymphocytes according to their affinity for insolubilized histamine. Principal differences between males and females. Clin. Exp. Immunol. 38: 166–172, 1979

    Google Scholar 

  • Thomas, E. D., Storb, R., Clift, R., Fefer, A., Johnson, F. L., Neiman, P. E., Lerner, K. G., Glucksburg, H., and Buckner, C. D.: Bone marrow transplantation. New Engl. J. Med. 292: 832–842, 1975

    Google Scholar 

  • Thomas, E. D., Buckner, C.D., Banaji, M., Clift, R. A.. Fefer, A., Flournoy, N., Goodell, B. W., Hickman, R. O., Lerner, K. G., Neiman, P. E., Jale, G. E., Sanders, J. E., Singer, J., Stevens, M., Storb, R., and Weiden, P. L.: One hundred patients with acute leukemia treated by chemotherapy, total body irradiation and allogenic marrow transplantation. Blood 49: 511–533, 1977

    Google Scholar 

  • Thomas, E. D., Sanders, J. E., Flournoy, N., Johnson, F. L., Buckner, C. D., Clift, R. A., Fefer, A., Goodell, B. W., Storb, R., and Weiden, P. L.: Marrow transplantation for patients with acute lymphoblastic leukemia in remission. Blood 54: 468–476, 1979

    Google Scholar 

  • Uphoff, D. E. and Law, L. W.: Genetic factors influencing irradiation protection by bone marrow. II. The histocompatibility-2- (h-2) locus. J. Natl. Cancer Inst. 20: 617–622, 1958

    Google Scholar 

  • van Bekkum, D. W., Balner, H., Dicke, K. A., Berg, F. G., vanden, Prinsen, G. H., and Hollander, C. F.: The effect of pretreatment of allogeneic bone marrow graft recipients with antilymphocyte serum on the acute graft-versus-host reaction in monkeys. Transplantation 13: 400–407 1972

    Google Scholar 

  • van Bekkum, D. W.: The double barrier in bone marrow transplantation. Semin. Hematol. 11: 325–340, 1974

    Google Scholar 

  • Vriesendorp, H. M.: Major histocompatibility complex of the dog. Erasmus University Rotterdam, The Netherlands, thesis, 1973

    Google Scholar 

  • Vriesendorp, H. M., Zurcher, C., Bull, R. W., Los, W. R. T., Meera Khan, P., van den Tweel, J. G., Zweibaum, A., and van Bekkum, D. W.: Take and graft versus host reactions of allogeneic bone marrow in tissue typed dogs. Transplant Proc. 7 (suppl. 1): 849–853, 1975a

    Google Scholar 

  • Vriesendorp, H. M., Bijnen, A. B., Zurcher, C., and van Bekkum, D. W.: Donor selection and bone marrow transplantation in dogs. In F. Kissmeyer-Nielsen (ed): Histocompatibility Testing, pp 963–971, Munksgaard, Copenhagen, 1975

    Google Scholar 

  • Vriesendorp, H. M., Grosse Wilde, H., and Dorf, M. E.: The major histocompatibility system of the dog. In D. Götze (ed.): The Major Histocompatibility System in Man and Animals, pp. 129–163, Springer-Verlag, Berlin, Heidelberg, New York, 1977

    Google Scholar 

  • Vriesendorp, H. M., Bijnen, A. B., van Kessel, A. C. M., Obertop, H., and Westbroek, D. L.: Minor histocompatibility systems in dogs. In S. J. Baum and G. D. Ledney (eds.): Experimental Hematology Today 1978, pp. 109–120, Springer-Verlag, New York-Heidelberg, 1978

    Google Scholar 

  • Vriesendorp, H. M. and, van Bekkum, D. W.: Bona marrow transplantation in the canine. In M. Shifine and F. D. Wilson (eds.): The Canine as a Biomedical Research Model, pp. 153–202, DOE Technical Information Center, Oak Ridge, 1980

    Google Scholar 

  • Vriesendorp, H. M.: The relative role of the DLA complex in bone marrow transplantation. In M. B. Zaleski, C. J. Abeyounis, and K. Kano (eds.): Immunobiology of the Major Histocompatibility Complex. p. 214, Karger, Basel, 1981

    Google Scholar 

  • Vriesendorp, H. M., Wagemaker, G., and van Bekkum, D. W.: Engraftment of allogeneic bone marrow. Transplant. Proc. 13: 643–648, 1981

    Google Scholar 

  • Wagemaker, G., Vriesendorp, H. M., and van Bekkum, D. W.: Successful bone marrow transplantation across major histocompatibility barriers in rhesus monkeys. Transplant. Proc. 13: 875–880, 1981

    Google Scholar 

  • Zurcher, C., Kessel, A. C. M. van, and Vriesendorp, H. M.: Graft versus host reactions in dogs after total body irradiation and bone marrow transplantation. p. 278, Annual Report REPGO, Rijswijk, The Netherlands, 1977

    Google Scholar 

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Vriesendorp, H.M., Klapwijk, W.M., Visser, T.P. et al. Alternatives to donor matching for control of graft-versus-host disease. Immunogenetics 15, 79–94 (1982). https://doi.org/10.1007/BF00375505

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  • DOI: https://doi.org/10.1007/BF00375505

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