AMPLIFICATION OF THE GRAFT-VERSUS-HOST REACTION BY CYCLOPHOSPHAMIDE -DEPENDENCE ON TIMING OF DRUG ADMINISTRATION

An experimental model, previously developed to study the combined effe ct of partial body irradiation and the graft-versus-host (GVH) reactio n, has been adapted to assay the amplification of the GVH reaction by cyclophosphamide (CY). The system has proved sensitive enough to detec t differences in the level of the GVH reaction produced by relatively small changes in pre-transplant conditioning. F-1 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 24h after CY inj ection resulted in 84% GVHD-related mortality with a mean survival tim e 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 e ffect was still detectable for an interval of 7 days between injection s but was no longer apparent when the interval was extended to 12 days .