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Blood, Vol. 94 No. 2 (July 15), 1999:
pp. 825-831
Keratinocyte Growth Factor Separates Graft-Versus-Leukemia Effects
From Graft-Versus-Host Disease
Oleg I. Krijanovski,
Geoffrey R. Hill,
Kenneth R. Cooke,
Takanori Teshima,
James M. Crawford,
Yani S. Brinson, and
James L.M. Ferrara
From the Department of Pediatric Oncology, Dana Farber Cancer
Institute, Children's Hospital, and Harvard Medical School, Boston,
MA; the Department of Pathology, Yale University School of Medicine,
New Haven, CT; and the Departments of Internal Medicine and Pediatrics,
Division of Hematology and Oncology, University of Michigan Cancer
Center, Ann Arbor, MI.
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) 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.
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