Keratinocyte growth factor separates graft-versus-leukemia effects from graft-versus-host disease
| Autor: | O I, Krijanovski, G R, Hill, K R, Cooke, T, Teshima, J M, Crawford, Y S, Brinson, J L, Ferrara |
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| Rok vydání: | 1999 |
| Předmět: |
Lipopolysaccharides
Fibroblast Growth Factor 7 Leukemia Experimental Tumor Necrosis Factor-alpha Graft vs Tumor Effect Drug Evaluation Preclinical Graft vs Host Disease Enzyme-Linked Immunosorbent Assay Epithelial Cells Recombinant Proteins Fibroblast Growth Factors Mice Inbred C57BL Mice Radiation Injuries Experimental Radiation Chimera Animals Humans Interleukin-2 Transplantation Homologous Female Intestinal Mucosa Growth Substances Fibroblast Growth Factor 10 Bone Marrow Transplantation T-Lymphocytes Cytotoxic |
| Zdroj: | Blood. 94(2) |
| ISSN: | 0006-4971 |
| Popis: | The major obstacles to successful outcome after allogeneic bone marrow transplantation (BMT) for leukemia remain graft-versus-host disease (GVHD) and leukemic relapse. Improved survival after BMT therefore requires more effective GVHD prophylaxis that does not impair graft-versus-leukemia (GVL) effects. We studied the administration of human recombinant keratinocyte growth factor (KGF) in a well- characterized murine BMT model for its effects on GVHD. KGF administration from day -3 to +7 significantly reduced GVHD mortality and the severity of GVHD in the gastrointestinal (GI) tract, reducing serum lipopolysaccharide (LPS) and tumor necrosis factor (TNF)alpha levels, but 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 treatment significantly decreased acute GVHD compared with control-treated allogeneic mice and resulted in a significantly improved leukemia-free survival (42% v 4%, P.001). KGF administration thus offers a novel approach to the separation of GVL effects from GVHD. |
| Databáze: | OpenAIRE |
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