Graft-versus-host disease can be separated from graft-versus-lymphoma effects by control of lymphocyte trafficking with FTY720

J Clin Invest. 2003 Mar;111(5):659-69. doi: 10.1172/JCI16950.


Graft-versus-host disease (GvHD) mediated by donor T cells recognizing host alloantigens is associated with beneficial graft-versus-tumor effects in recipients of allogeneic hematopoietic cell transplants. Since leukemias and lymphomas reside largely within the lymphohematopoietic system, we have proposed that the desired graft-versus-leukemia or graft-versus-lymphoma effect can be separated from the complication of GvHD by confinement of the graft-versus-host alloresponse to the lymphohematopoietic tissues. Since the new sphingosine-1-phosphate receptor agonist immunosuppressive drug FTY720 leads to trapping of T cells in secondary lymphoid tissues, we evaluated the possibility that this drug could diminish GvHD, a disease involving epithelial target tissues, while permitting a beneficial alloresponse to take place within the lymphohematopoietic system, leading to graft-versus-lymphoma effects. We demonstrate here that FTY720 markedly reduces GvHD in a clinically relevant, haploidentical strain combination, while permitting antitumor effects against a T cell lymphoma of unshared host MHC haplotype to proceed unhindered. These results establish a potential new immunotherapeutic approach to separating graft-versus-leukemia effects from GvHD.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Transplantation
  • Cell Movement / drug effects
  • Female
  • Fingolimod Hydrochloride
  • Graft vs Host Disease / drug therapy*
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / pathology
  • Graft vs Tumor Effect / drug effects*
  • Immunosuppressive Agents / pharmacology*
  • Lymphocyte Activation / drug effects
  • Lymphocytes / drug effects*
  • Lymphocytes / physiology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Propylene Glycols / pharmacology*
  • Sphingosine / analogs & derivatives
  • T-Lymphocytes, Cytotoxic / immunology


  • Immunosuppressive Agents
  • Propylene Glycols
  • Fingolimod Hydrochloride
  • Sphingosine