FTY720 does not abrogate acute graft-versus-host disease in the dog leukocyte antigen-nonidentical unrelated canine model.
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.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Richard S
RS
Lee
Christian S
CS
Kuhr
George E
GE
Sale
Eustacia
E
Zellmer
William J
WJ
Hogan
Rainer
R
Storb
Marie-Térèse
MT
Little
D000208:Acute Disease; D000818:Animals; D004285:Dogs; D000068876:Fingolimod Hydrochloride; D006086:Graft vs Host Disease / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D018655:Lymphocyte Count; D011409:Propylene Glycols / Q000009:adverse effects / Q000494:pharmacology*; D012008:Recurrence; D012720:Severity of Illness Index; D013110:Sphingosine / Q000031:analogs & derivatives
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine