Bone marrow transplantation in the busulfan-treated rat. I. Effect of cyclophosphamide and rabbit antirat thymocyte serum as immunosuppression.

It was previously shown that lethal doses of busulfan (BU) were not immunosuppressive in the rat. In the present studies the effect of rabbit antirat thymocyte serum (RARTS) and cyclophosphamide (CY) as immunosuppressive preparation for marrow allografts in the rat given supralethal doses of BU was investigated. Lewis or LBNF rats were given RARTS for 4-12 consecutive daily doses. They were given a supralethal dose of BU in addition on the last day of RARTS administration. Ag-B-incompatible (ACI). Ag-B-compatible (F344), or syngeneic marrow was infused 24 hr later. In general, RARTS was not toxic to the marrow graft and permitted engraftment of Ag-B-incompatible and compatible marrow. All animals given Ag-B-incompatible marrow and Ag-B-compatible marrow that survived to day 21 were shown to be chimeric, but all those with incompatible marrow subsequently died from severe graft-versus-host disease (GVHD). In other experiments Lewis or LBNF1 rats were given Ag-B-incompatible (ACI) and compatible (F344) marrow after a supralethal dose of BU and single graded doses of CY. Doses of CY as low as 25-50 mg/kg provided sufficient immunosuppression to allow allogeneic engraftment. Transient chimerism was seen up to doses of 100 mg/kg of CY. Permanent chimerism was seen with doses of CY from 150 to 250 mg/kg. The incidence of lethal GVHD increased in parallel with the percentage of animals that were demonstrated to be chimeric. Mild but transient GVHD was seen with Ag-B-compatible marrow given to Lewis rats.