by Oleg I. Krijanovski, Geoffrey R. Hill, Kenneth R

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Keratinocyte Growth Factor Separates Graft-Versus-Leukemia Effects From Graft-Versus-Host Disease by Oleg I. Krijanovski, Geoffrey R. Hill, Kenneth R. Cooke, Takanori Teshima, James M. Crawford, Yani S. Brinson, and James L.M. Ferrara Blood Volume 94(2):825-831 July 15, 1999 ©1999 by American Society of Hematology

Small bowel histology 5 days after BMT Small bowel histology 5 days after BMT. (A) Allogeneic control mouse, exhibiting severe villus blunting, extensive crypt destruction with no appreciable regenerative response, and a moderate lamina propria inflammatory infiltrate. Small bowel histology 5 days after BMT. (A) Allogeneic control mouse, exhibiting severe villus blunting, extensive crypt destruction with no appreciable regenerative response, and a moderate lamina propria inflammatory infiltrate. (B) Allogeneic mouse treated with KGF from day -3 to +5 exhibiting moderate villus blunting, prominent crypt regenerative features, and minimal lamina propria inflammatory infiltrate. Features in syngeneic control mice (not shown) were identical to those in KGF allogeneic animals. Oleg I. Krijanovski et al. Blood 1999;94:825-831 ©1999 by American Society of Hematology

KGF reduces GVHD mortality and morbidity in allogeneic BMT KGF reduces GVHD mortality and morbidity in allogeneic BMT. Recipients were transplanted with 5 × 106 bone marrow cells and 0.5 × 106 splenic T cells from allogeneic (B6) or syngeneic (B6D2F1) donors after 1,550 cGy of TBI. KGF (Amgen) or control diluent wa... KGF reduces GVHD mortality and morbidity in allogeneic BMT. Recipients were transplanted with 5 × 106 bone marrow cells and 0.5 × 106 splenic T cells from allogeneic (B6) or syngeneic (B6D2F1) donors after 1,550 cGy of TBI. KGF (Amgen) or control diluent was given subcutaneously from either day -3 to day 0 or day -3 to +7. Syngeneic BMT (n = 22, - - - ), control diluent-treated allogeneic BMT (n = 26, - · · - ), KGF-treated (day - 3 to 0) allogeneic BMT (n = 16, ), KGF-treated (day -3 to +7) allogeneic BMT (n = 18, ). (A) Survival. Control-treated allogeneic BMT recipients versus KGF-treated (both treatment schedules) and syngeneic BMT recipients (P < .01 by Mantel Cox logrank test). (B) GVHD clinical score. Animals were scored for clinical GVHD by five parameters as described in Materials and Methods. GVHD severity (mean ± standard error [SE]) was significantly less in animals receiving KGF from day -3 to +7 than those receiving KGF from day -3 to 0 and control-treated animals from day 21 onwards (P < .05) and significantly higher than in syngeneic BMT recipients (P < .05). Data represent results combined from two similar experiments. Oleg I. Krijanovski et al. Blood 1999;94:825-831 ©1999 by American Society of Hematology

Preservation of allogeneic GVL effects in KGF-treated mice. Preservation of allogeneic GVL effects in KGF-treated mice. B6D2F1 recipients were conditioned and transplanted as in Fig 1with the addition of 5,000 P815 tumor cells to the bone marrow inoculum at day 0. Recipients of TCD bone marrow or bone marrow plus T cells from allogeneic B6 donors were treated with KGF or control diluent from day -3 to +7 as described in Materials and Methods. Results are represented as Kaplan-Meier cumulative survival estimates from two similar experiments. Control diluent-treated TCD recipients (, n = 11), KGF-treated TCD recipients ( - - - , n = 6), control allogeneic BMT recipients ( – · · – , n = 28), KGF allogeneic BMT recipients (, n = 17). KGF versus control (allogeneic BMT groups), P < .0001. Oleg I. Krijanovski et al. Blood 1999;94:825-831 ©1999 by American Society of Hematology