FTY720 does not abrogate acute graft-versus-host disease in the dog leukocyte antigen-nonidentical unrelated canine model

Richard S. Lee, Christian S. Kuhr, George E. Sale, Eustacia Zellmer, William Hogan, Rainer Storb, Marie Térèse Little

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background. Acute graft-versus-host disease (GVHD) remains a significant impediment to successful hematopoietic stem-cell transplantation (HSCT). Here, we examined the effectiveness of 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol hydrochloride (FTY720), an immunosuppressant that retraffics activated lymphocytes to secondary lymphoid organs, for the treatment of acute GVHD in an established dog leukocyte antigen-nonidentical unrelated canine HSCT model. Methods. Dogs were given HSCT after conditioning with 920 cGy total body irradiation. The dogs received methotrexate 0.4 mg/kg/day on days 1, 3, 6, and 11 and FTY720 (5 mg/kg/day orally) after developing GVHD. Results. Five of six dogs achieved engraftment, developed acute GVHD, and were treated with FTY720. FTY720 resulted in a profound decrease in lymphocytes and a temporary mitigation of clinical GVHD; however, GVHD recurred in all dogs. Four of five dogs were euthanized because of severe GVHD and the fifth because of severe inanition associated with moderate GVHD. Conclusions. Compared with controls, treatment of GVHD with FTY720 did not control this complication or significantly increase survival.

Original languageEnglish (US)
Pages (from-to)1155-1158
Number of pages4
JournalTransplantation
Volume76
Issue number8
DOIs
StatePublished - Oct 27 2003
Externally publishedYes

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Graft vs Host Disease
HLA Antigens
Canidae
Dogs
Hematopoietic Stem Cell Transplantation
Transplantation Conditioning
Lymphocytes
Fingolimod Hydrochloride
Whole-Body Irradiation
Immunosuppressive Agents
Methotrexate
Therapeutics

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

FTY720 does not abrogate acute graft-versus-host disease in the dog leukocyte antigen-nonidentical unrelated canine model. / Lee, Richard S.; Kuhr, Christian S.; Sale, George E.; Zellmer, Eustacia; Hogan, William; Storb, Rainer; Little, Marie Térèse.

In: Transplantation, Vol. 76, No. 8, 27.10.2003, p. 1155-1158.

Research output: Contribution to journalArticle

Lee, Richard S. ; Kuhr, Christian S. ; Sale, George E. ; Zellmer, Eustacia ; Hogan, William ; Storb, Rainer ; Little, Marie Térèse. / FTY720 does not abrogate acute graft-versus-host disease in the dog leukocyte antigen-nonidentical unrelated canine model. In: Transplantation. 2003 ; Vol. 76, No. 8. pp. 1155-1158.
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