Abstract
We have tested ifosfamide and ACNU for their effectiveness in preventing graft rejection following allogeneic bone marrow transplantation. The engraftment-promoting potency of both was compared to that of the standard agent cyclophosphamide. LEW rats received a lethal dose (35 mg/kg) of busulfan followed by injection of 1 x 10(8) (CAP x LEW) F1 marrow cells, which are unable to induce a graft vs host reaction in LEW recipients. Rejection of the marrow graft was assessed by monitoring haematocrit and granulocyte count either until death of the animal or until day 80. Surviving animals received a donor-type skin graft to confirm the persistence of allogeneic haematopoiesis. Because of its weak immunosuppressive properties, busulfan by itself is unable to allow engraftment of allogeneic marrow. Therefore, ifosfamide and ACNU and cyclophosphamide as the standard agent could be tested for their capacity to prevent marrow graft rejection. The following rejection rates were observed: cyclophosphamide: 30 mg/kg 100%, 60 mg/kg 60%, 90 mg/kg 20%, 120 mg/kg and 180 mg/kg 0%; ACNU: 3, 5, 7, and 10 mg/kg 100%, 15 mg/kg 45%, 20 and 30 mg/kg 0%; ifosfamide: 60-120 mg/kg 100%, 180 mg/kg 68%, 240 and 360 mg/kg 0%. Thus, 240 mg/kg ifosfamide or 20 mg/kg ACNU is nearly equivalent to the standard dose of 120 mg/kg cyclophosphamide in engraftment-promoting potency in allogeneic bone marrow transplantation.