- Objective. To determine whether thalidomide is an effective prophylactic agent against acute graft-versus-host disease (GVHD) and whether it exerts an effect on graft-versus-leukemia (GVL) reactivity, the drug was administered to leukemic mice that were exposed to allogeneic bone marrow transplantation. Methods. Mice (BALB/c 3 C57BL/6) F1 were inoculated with 107 B cell leukemia cells (BCL1) and conditioned with total body irradiation followed by reconstitution with bone marrow plus splenic cells harvested from C57BL/6 mice. After transplant, mice were treated with oral thalidomide (20 mg/kg/day) for a period of 10 days. Results. Stable chimerism was documented in all recipients with $73% (mean) donor-type C57 cells. In this semi-allogeneic murine model, thalidomide failed to prevent or alleviate the acute GVHD symptoms; however, the drug did not impair GVL reactivity. The antileukemia allogeneic effect was similar in the thalidomide and non-thalidomide-treated animals. Comparison of the GVL reactivity occurring in the allogeneically transplanted groups with that in the syngeneic recipients revealed a significant difference (P 5 0.001). Conclusions. Although thalidomide did not exert any effect against acute GVHD, the fact that the GVL reactivity was spared holds promise for its use as a treatment modality in chronic GVHD.