Secondary tumors after high-dose cyclophosphamide and total-body irradiation followed by bone marrow transplantation in a rat model for human acute myelocytic leukemia (BNML).

Brown Norway (BN) rats carrying a transplantable acute myelocytic leukemia (BNML) were given a supralethal combination of cyclophosphamide (80-100 mg/kg i.p.) and total-body irradiation (9.0 Gy gamma rays or 8.5 Gy X-rays) followed by isologous bone marrow transplantation. Of 110 long-term survivors (greater than 95 days), 40 (45%) died of a secondary malignancy at a median posttreatment age of 450 days. At a comparable age, non-treated control BN rats show a spontaneous tumor incidence of 5% only, which increased to 83% during the aging process. Thus the latency period for the appearance of tumors was impressively shortened. Tumors of neurogenic origin and acute leukemias were the most prominent types, in contrast with non-treated control rats.