GVL effect obtained by delayed GCV administration.

(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 cells at the time of grafting. GCV was administered from day 6 to day 8 after graft (black square; n = 10); GVL effect was induced in GVHD mice receiving P815 cells and treated with GCV from day 3½ after graft (white square; n = 10) or from day 6 after graft (white circle; n = 10). One group of mice also received CsA treatment from day −2 until day 10 after the graft and GCV treatment from day 6 to day 8 (white triangle; n = 5). Results are presented as Kaplan-Meier survival curves of cumulative data of 2 independent experiments. (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. GCV was administered at day 6 (GCV d6-8; n = 10). Two groups of mice received P815 leukemia cells at the time of transplantation and were treated by GCV starting on day 3½ (P815 + GCV d3½-d5 1/2; n = 3) or day 6 (P815 + GCV d6-8; n = 8) after the graft, respectively. Histograms indicate the mean histopathological score for each group. The Fisher test was used for ANOVA; P < .05 for P815 + GCV d3½-5½ versus P815 + GCV d6-8.