Repifermin (keratinocyte growth factor-2) reduces the severity of graft-versus-host disease while preserving a graft-versus-leukemia effect

Shawn G. Clouthier, Kenneth R. Cooke, Takanori Teshima, Kathleen P. Lowler, Chen Liu, Kevin Connolly, James L.M. Ferrara

Research output: Contribution to journalArticlepeer-review

Abstract

Graft-versus-host disease (GVHD) is the principal complication after allogeneic bone marrow transplantation (BMT). Reductions in systemic GVHD are frequently associated with a corresponding diminishment of the graft-versus-leukemia (GVL) response. In this study, we tested the effects of a novel recombinant human keratinocyte growth factor, repifermin (keratinocyte growth factor-2), on the induction of GVHD in a well-defined murine BMT model (B6 → B6D2F1). Administration of repifermin (5 mg/kg/d) to allogeneic BMT recipients resulted in a significant decrease in both systemic GVHD and target organ histopathology. Repifermin treatment also reduced serum levels of tumor necrosis factor α and lipopolysaccharide compared with control mice. In contrast, repifermin did not affect T-cell proliferation, cytokine production, or cytotoxic responses to host antigens. When 2000 host-derived P815 (H-2d) leukemia cells were added to the bone marrow inoculum, repifermin preserved GVL effects and resulted in significantly delayed mortality compared with control-treated allogeneic BMT recipients. Collectively, these data suggest that repifermin administration may represent a novel strategy to separate the toxicity of GVHD from the beneficial GVL effects after allogeneic BMT.

Original languageEnglish (US)
Pages (from-to)592-603
Number of pages12
JournalBiology of Blood and Marrow Transplantation
Volume9
Issue number9
DOIs
StatePublished - Sep 2003
Externally publishedYes

Keywords

  • Bone marrow transplantation
  • Cytokines
  • FGF-10
  • FGF-7
  • Graft-versus-host disease
  • Graft-versus-leukemia
  • Keratinocyte growth factor-1
  • Keratinocyte growth factor-2
  • Repifermin

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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