The carcinogenic risk of high dose total body irradiation in non-human primates

Purpose: High dose total body irradiation (TBI) in combination with chemoth erapy, followed by rescue with bone marrow transplantation (BMT), is increa singly used for the treatment of haematological malignancies. With the incr easing success of this treatment and its current introduction for treating refractory autoimmune diseases the risk of radiation carcinogenesis is of g rowing concern. Studies on tumour induction in non-human primates are of re levance in this context since the response of this species to radiation doe s not differ much from that in man. Materials and methods: Since the early sixties, studies have been performed on acute effects in Rhesus monkeys and the protective action of bone marro w transplantation after irradiation with X-rays (average total body dose 6. 8 Gy) and fission neutrons (average dose 3.4 Gy). Of those monkeys, which w ere irradiated and reconstituted with autologous bone marrow, 20 animals in the X-irradiated group and nine animals in the neutron group survived more than 3 years. A group of 21 non-irradiated Rhesus monkeys of a comparable age distribution served as controls. All animals were regularly screened fo r the occurrence of neoplasms. Complete necropsies were performed after nat ural death or euthanasia. Results: At post-irradiation intervals of 4-21 years an appreciable number of tumours was observed. In the neutron irradiated group eight out of nine animals died with one or more malignant tumours. In the X-irradiated group this fraction was 10 out of 20. The tumours in the control group, in seven out of the 21 animals, appeared at much older age compared with those in th e irradiated cohorts. The histogenesis of the rumours was diverse with a pr eponderance of renal carcinoma, sarcomas among which osteosarcomas, and mal ignant glomus rumours in the irradiated groups. Conclusions: When corrected for competing risks, the carcinogenic risk of T BI in the Rhesus monkeys is similar to that derived from the studies of the Japanese atomic bomb survivors. The increase of the risk by a factor of 8, observed in the monkeys, indicates that patients are likely to develop mal ignancies more frequently and much earlier in life after TBI than non-expos ed individuals. This finding underlines the necessity of regular screening of long-term surviving patients subjected to TBI and BMT. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.