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 J. Hogan, Rainer Storb, Marie Térèse Little

Research output: Contribution to journalArticle

21 Scopus citations

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

ASJC Scopus subject areas

  • Transplantation

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