Pharmacological inhibition of Sirt-1 with Ex-527 alleviates aGVHD while preserving the GVL activity. (A-B) GVHD experiments: Lethally irradiated (700 cGy) BALB/c mice underwent transplantation with 5 × 10⁶ TCD-BM alone or plus 0.7 × 10⁶ CD25⁻ T cells per mouse isolated from WT and administered with either phosphate-buffered saline or 2 mg/kg Ex-527/mouse/day daily for 3 weeks. (A) GVHD clinical score. (B) Survival (n = 10 mice/group). (C-G) GVL experiments: (C) Bar graph shows quantified percentages of MLL-AF9-GFP in the recipients’ peripheral blood on days 20, 30, 45, and 60 (n = 10 mice/group). (D) Survival of recipient mice was monitored. (E-G) Lethally irradiated (1100 cGy, split dose) BDF1 recipients were transplanted with 5 × 10⁶ TCD-BM and 5 × 10³ P815 mastocytoma plus 3 × 10⁶ CD25⁻ T cells. Recipients were monitored for tumor burden. (E) Representative images of tumor growth measured by bioluminescent imaging. (F) Tumor mortality and (G) mouse survival were monitored. Data were combined from 2 independent experiments (n = 10 mice/group). Log-rank (Mantel-Cox) test was used to compare the tumor mortality and survival. *P < .05; **P < .01; ***P < .001.