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By Fritz H Bach; Robert A Good

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Experimental Research for New Means to Control GVH References 33 34 45 50 52 60 I. The First Bone Marrow Grafts in Man after Irradiation Exposure When we received, in 1958 (Mathé et al, 1959a), six human victims of total body irradiation (TBI), we were working on bone marrow transplantation in mice (Mathé and Bernard, 1958; Mathé et al, 1971a). We knew at the time from our observations and from numerous available experimental data, especially from Barnes and Loutit (1956). Van Bekkum et al (1956), Congdon (1959), Trentin (1957), and Uphoff and Law ( 1959 ) that : ( 1 ) an allogeneic marrow transplantation is often followed by a successful graft in animals irradiated in toto at lethal or sublethal doses because of the immune insufficiency induced by total irradiation at that dose; (2) this graft is usually followed by so-called secondary disease (SD), often lethal; and (3) this disease is induced if not entirely explained by the graft-versus-host reaction (GVH).

Finally, we made up our minds regarding the 80-100% lethality of the doses received by five of the patients. This decision was based on hematological observations and clinical decompensation. Later comparison of these hematological data with data obtained after deliberate irradiation showed that we were right (Mathé, 1962). So we transplanted allogeneic marrow from voluntary donors to each patient on different days following irradiation, when each one became clinically decompensated, and obtained a restoration appearing at a time depending on the day they underwent engraftment.

Siegel, S. , Schreiber, A. , Goldstein, I. , and Henderson, E. S. (1973). Protected environments: A prospective controlled study of their utility in the therapy of acute leukemia. N. Engl. J. Med. 288, 477-483. Lochte, H. , Levy, A. , Guenther, D. , Thomas, E. , and Ferrebee, J. W. ( 1962 ). Prevention of delayed foreign marrow reaction in lethally irradiated mice by early administration of methotrexate. Nature 196, 1110-1111. Mathé, G. ( 1 9 6 1 ) . Secondary syndrome, a stumbling block in the treatment of leukaemia by whole body irradiation and transfusion of allogeneic haemopoietic cells.

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