Inhibition of hedgehog signaling by LDE223 is well tolerated and prevents the clinical features of sclerodermatous cGVHD. (A) Preventive treatment with LDE223 impeded weight loss after alloBMT and resulted in a significantly higher body weight. (B) The clinical composite score for cutaneous cGVHD was significantly lower in mice treated with LDE223 in a preventive manner compared with sham-treated mice. (C) LDE223 prevented the histologic changes of experimental sclerodermatous cGVHD. Preventive regimen of LDE223 reduced dermal thickening, decreased the hydroxyproline content of the skin (D) and diminished the differentiation of resting fibroblasts into myofibroblasts (E) compared with sham-treated mice. Histologic analyses were performed at day 42 after transplantation. Six mice per group were analyzed. synBMT indicates syngeneic controls; and alloBMT, mice receiving alloBMT.