Keratinocyte growth factor separates graft-versus-leukemia effects from graft-versus-host disease

The major obstacles to successful outcome after allogeneic bone marrow tran splantation (BMT) for leukemia remain graft-versus-host disease (GVHD) and leukemic relapse. Improved survival after BMT therefore requires more effec tive GVHD prophylaxis that does not impair graft-versus-leukemia (GVL) effe cts, We studied the administration of human recombinant keratinocyte growth factor (KGF) in a well-characterized murine BMT model for its effects on G VHD. KGF administration from day -3 to +7 significantly reduced GVHD mortal ity and the severity of GVHD in the gastrointestinal(GI) tract, reducing se rum lipopolysaccharide (LPS) and tumor necrosis factor (TNF)alpha levels, b ut preserving donor T-cell responses (cytotoxic T lymphocyte [CTL] activity , proliferation, and interleukin [IL]-2 production) to host antigens. When mice received lethal doses of P815 leukemia cells at the time of BMT, KGF t reatment significantly decreased acute GVHD compared with control-treated a llogeneic mice and resulted in a significantly improved leukemia-free survi val (42% v 4%, P < .001). KGF administration thus offers a novel approach t o the separation of GVL effects from GVHD. (C) 1999 by The American Society of Hematology.