Amplification of the graft-versus-host reaction by cyclophosphamide: dependence on timing of drug administration.

An experimental model, previously developed to study the combined effect of partial body irradiation and the graft-versus-host (GVH) reaction, has been adapted to assay the amplification of the GVH reaction by cyclophosphamide (CY). The system has proved sensitive enough to detect differences in the level of the GVH reaction produced by relatively small changes in pre-transplant conditioning. F1 hybrid mice treated with either CY 60 mg/kg or allogeneic (parental) lymphoid cells (ALC, 20 x 10(6)) had 100% survival. In contrast, ALC given 24 h after CY injection resulted in 84% GVHD-related mortality with a mean survival time of 18 days. Amplification of the GVH reaction by CY was also seen in terms of splenomegaly and immunosuppression. Separation of CY and ALC injection by an interval longer that 24 h reduced the severity of GVH reaction but some amplification was still observed. Based on several GVHD-related criteria, experimental groups with a 2 or 4 day interval between CY and ALC injection had approximately the same response, an effect was still detectable for an interval of 7 days between injections but was no longer apparent when the interval was extended to 12 days.