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Updated: Jun 30, 2026
Induction of Graft-versus-host Disease and In Vivo T Cell Monitoring Using an MHC-matched Murine Model
Published on: August 29, 2012
FTY720 does not abrogate acute graft-versus-host disease in the dog leukocyte antigen-nonidentical unrelated canine
Richard S Lee1, Christian S Kuhr, George E Sale
1Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
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.
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