Two juvenile pigtailed macaques (animals 1 and 2) received total body irradiation (TBI) followed by autologous stem cell transplantation, by a procedure known to be well tolerated by baboons. In this procedure, the TBI consisted of treatment on two consecutive days with 255cGy on one side, followed after 1-2 min by a similar dose on the other side. The two pigtailed macaques showed rapid haematopoietic engraftment, but succumbed either to systemic cytomegalovirus (CMV) infection and necrotising colitis or to haemorrhagic cystitis and tubulointerstitial nephritis. For four further pigtailed macaques (animals 3-6) the radiation procedure was changed to four equal doses of 255cGy, given 6-12 h apart. Animals 4-6 all showed engraftment and survived for long periods (>218 days), with no, or only minor treatable, complications. Animal 3 failed to show engraftment and succumbed to radiation-induced vascular lesions and severe multiorgan haemorrhages. The results suggest that pigtailed macaques have a lower tolerance threshold than baboons, rhesus macaques or human beings to TBI, the adverse effects of TBI being indistinguishable from those seen in human patients. The results also suggest that a hyperfractionated radiation procedure can prevent radiation-induced morbidity and mortality in pigtailed macaques.
Copyright 2004 Elsevier Ltd.