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, James L.M. Ferrara

Research output: Contribution to journalArticle

Abstract

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)α 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% v4%, P < .001). KGF administration thus offers a novel approach to the separation of GVL effects from GVHD.

Original languageEnglish (US)
Pages (from-to)825-831
Number of pages7
JournalBlood
Volume94
Issue number2
StatePublished - Jul 15 1999

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Krijanovski, O. I., Hill, G. R., Cooke, K. R., Teshima, T., Crawford, J. M., Brinson, Y. S., & Ferrara, J. L. M. (1999). Keratinocyte growth factor separates graft-versus-leukemia effects from graft-versus-host disease. Blood, 94(2), 825-831.