Bone marrow transplantation in a BN rat model of acute myelogenous leukemia (AML)

A rat model of acute myelogenous leukemia is described. The leukemia originally induced by 7,12 dimethylbenzanthracine in the Brown Norway (BN) rat can be transferred by the inoculation of leukemic blasts intravenously into normal female BN rats. The survival of animals given 1-100 × 10⁶ leukemic blasts ranges from 15 to 25 days following tumor transfer, with the lowest number of cells injected giving the longest survival times. If 1 × 10⁶ blasts are injected and, 2 weeks later, groups of rats receive lethal doses of cyclophosphamide (CY), busulfan (BU) or total body irradiation (TBI) followed 24 h later by a syngeneic marrow graft, only animals which receive the CY conditioning survive more than 2 weeks (survival > 100 days) following the transplant. All other animals die with marrow failure (early death) or florid leukemia. Preliminary studies with an allogeneic (ACI marrow graft given to the BN rat) marrow graft suggests that leukemic rats may accept a histoincompatible graft without leukemic relapse following cyclophosphamide conditioning and postgraft immunosuppression. The anti-leukemic effect of cyclophosphamide, therefore, appears to be greater for this disease than is busulfan or total body irradiation.