Hematologic Events as Dosimeters in Human Total-Body Irradiation

Abstract

Knowledge of the pathogenesis of human irradiation injury has accumulated through the years from several sources, including extrapolations from animal experiments, studies of patients given local therapeutic radiation, details of atomic warfare casualties, and studies of victims of industrial accidents involving ionizing radiation. Data from each of these sources, although contributing to our understanding of the subject, suffer obvious limitations. For example, the human body would be expected to show a different response to total-body irradiation than to local irradiation. Data derived from war and industrial casualties suffer because the exact amount of radiation received is unknown. In view of such limitations, observations of post-irradiation events in patients given total-body irradiation in known amounts seem pertinent. During the past few years we have studied clinical events in 18 patients receiving therapeutic, uniform, total-body gamma irradiation in doses ranging from 225 to 1,500 r (1). Of these patients, 6 were selected for detailed hematologic analysis on the basis of essentially normal blood counts prior to treatment and a known amount of radiation delivered in a single dose. Although the number of patients is small, results suggest rough correlation between the rate and degree of depression of formed blood elements and the amount of radiation received. Particularly noteworthy is evidence suggesting that the reticulocyte may be most important as an early indicator of lethal total-body irradiation. Methods Barbiturate and phenothiazine drugs were given in standard doses prior to irradiation. Autologous bone marrow was administered as an adjunct procedure to the patient who received 900 r and to 2 of the patients who received 450 r. Marrow was obtained by multiple aspiration under general anesthesia one to two days before irradiation. This was stored in tissue-culture medium (NCTC 109) at 4° C. and infused intravenously within three days after irradiation. Homologous bone marrow was infused intravenously into the patient who received 1,500 r. Radiation was administered by a specially designed, multiple-source gamma unit, which has been described previously (2). Essentially the patient is placed in a horizontal cylinder of 1/8-inch aluminum, 6 feet long and 32 inches in diameter. By means of a pneumatic system, the cylinder is surrounded by 60 encapsulated sources of Co60 arranged in an attempt to approach 4 π geometry. The original activity of 2,500 curies of Co60 had decayed to about 1,500 curies at the time of treatment. Dose rates varied from 7.5 to 30 r/min. measured as a “mid-air dose” (1). Standard methods were used for the hematologic studies. Platelets were counted by a direct method (3). Reticulocytes were stained with new methylene blue and enumerated per 2,000 red cells.