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. These tumors included two leiomyosarcomas of the mesentery, four adenocarcinomas of the breast, prostate and ovary, two mastocytomas, one hypernephroma, perianal gland carcinoma, seminoma, Brenner tumor, and an oligodendroglioma. Fifty-four malignancies were seen in 44 control dogs. These included 12 mammary carcinomas, 12 thyroid carcinomas, six lymphomas, two malignant melanomas, and a number of other solid tumors. 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 less than 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.