Absence of GVL effect after early GCV treatment.

(A) Experimental GVHD was induced by B6 TK T cells injected together with B6 TCD-BM cells in lethally irradiated B6 × D2 F₁ recipient mice. Leukemic challenge was performed by intravenous injection of 2 × 10³ P815 (H-2^d) mastocytoma cells at the time of grafting. In the absence of treatment (black circle; n = 10) GVHD is lethal. GCV is administered by continuous subcutaneous infusion from day 0 until day 7 after graft (white square; n = 4) or by 5 intraperitoneal injections every 12 hours beginning 24 hours after BMT (white triangle; n = 6). For the leukemia control group, B6 × D2 F₁mice were grafted with B6 TCD-BM plus P815 cells (white circle; n = 5). The experimental group is represented by B6 × D2 F₁ mice grafted with B6 TCD BM plus B6 TK T cells plus P815 cells and treated by GCV from day 1 to day 3 after graft (black square; n = 8). Results are presented as Kaplan-Meier survival. (B) Histopathologic liver score after semiallogeneic BMT. Histopathologic examination and grading of GVHD of liver from mice were performed 65 to 75 days after transplantation. GVHD control mice did not receive GCV treatment (no GCV; n = 2) and were killed at day 19 with clinical signs of GVHD (body weight below 13 g, hunching). GCV treatment consisted of continuous subcutaneous administration from day 0 to day 7 after graft (GCV d0-7; n = 4) or of 5 intraperitoneal injections every 12 hours beginning 24 hours after graft (GCV d1-3; n = 5). Histograms indicate the mean histopatological score for each group. The Fisher test was used for the ANOVA;P < .05 for GVHD group versus all other groups.