High-Dose Total-Body Irradiation and Autologous Marrow Reconstitution in Dogs: Dose-Rate-Related Acute Toxicity and Fractionation-Dependent Long-Term Survival

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Abstract
Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts to avoid death from marrow toxicity. Acute and delayed non-marrow toxcities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy[gray]/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 h for 3 increments/day. Acute toxicity and early mortality (< 1 mo.) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16 and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5 and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.05 Gy/min, 2/5 and 3/3 dogs died acutely; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died acutely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; .ltoreq. day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (day 18) was given fractionated and 2 (days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 mo.; 8 of these had single-dose TBI (10-14 Gy) and all died within 7 mo. of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250-500 days after irradiation. Fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors.