The capability of producing a marked and prolonged lymphopenia by extracorporeal irradiation (ECI) of the blood (1, 2), the prolongation in rejection of skin grafts (3), the development of a cobalt-60 irradiator to supplant the X-ray machine (4), and semipermanent Teflon-Silastic arteriovenous shunts have become realities. In the original experiments a transit dose of 900 rads was adapted, since the work of Trowell (5) led us to believe that this dose would approximate the 100 % lethal dose for lymphocytes. However, in some of the experiments with continuous ECI of the blood for 36 to 72 hours, severe hemolysis developed, owing to radiation injury of the red cells. This necessitated a fuller understanding of the factors that might contribute to an accumulation of sufficient dose to the red cells to produce hemolysis before ECI could be extended to the study and treatment of human disease. It had been demonstrated by Slatkin et al. (6) that one can estimate the dose distribution to any items that remain within the blood stream during ECI of the blood from the volume of the blood in the total bypass, the blood volume, the transit dose, and the total duration of ECI. By applying these mathematical principles to the specific cases in which hemolysis was induced, it was found that, when a substantial fraction of red cells had accumulated a dose in excess of 100,000 rads, hemolysis commenced. These studies (7) have in fact shown that 100,000 rads delivered to red cells in vitro will cause a major portion of them to be destroyed promptly on subsequent autotransfusion of the labeled cells into the donor. Prior to application of ECI in the treatment of leukemia in man or in the preparation of patients for homotransplantation of organs, one must know the best ECI treatment schedule to suppress the radiosensitive lymphocytes in the blood and how to minimize injury to the radioresistant red cells, because the ultimate duration of therapy
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