Increased incidence of malignant tumors in dogs after total body irradiation and marrow transplantation

One hundred fifty-three dogs were given 6.1-21.3 Gy total body irradiation at 0.02-0.2 Gy/minute delivered from two opposing cobalt sources followed by allogeneic (131 dogs) or autologous (22 dogs) marrow grafts and observed for 6-127 (median 33) months. The incidence of malignant tumors in radiation chimeras was compared to that in 242 untreated dogs observed for 6-188 (median 81) months. Thirteen malignancies were observed in 11 radiation chimeras. Fifty-four malignancies were seen in 44 control dogs. On the basis of time-dependent Cox regression analysis, radiation chimeras had an estimated relative risk of developing a malignancy that was 5-fold higher than in control dogs (p < 0.001). No tumor has yet been observed in a group of 15 chimeras conditioned by cyclophosphamide or dimethyl busulfan and followed for 6-97 (median 24) months. The increased risk of cancer among canine radiation chimeras suggests that high-dose total body irradiation may increase the risk of developing a malignancy and should be avoided whenever possible in the conditioning for marrow transplantation of human patients with nonmalignant diseases