What role for FTY720, a novel immunosuppressive agent, in canine nonmyeloablative hematopoietic stem cell transplantation?
BACKGROUND
Stable mixed donor/host hematopoietic chimerism was almost uniformly achieved in dogs given 200 cGy total body irradiation (TBI) before, and a short course of immunosuppression after, transplantation of marrow from dog leukocyte antigen-identical littermates, but was transient when the TBI dose was decreased to 100 cGy. Here, we examined whether stable engraftment could be achieved in five dogs given FTY720 (days -5 and -4), followed by 100 cGy TBI, dog leukocyte antigen-identical marrow grafts, and mycophenolate mofetil/cyclosporine.


CONCLUSIONS
Although all five dogs showed initial engraftment, four dogs rejected their grafts within 11 weeks, whereas one dog was euthanized on day 17 due to enteritis. This was not different from the control dogs not given FTY720 (P=0.32). Thus, FTY720 failed to enhance allogeneic engraftment in this model, perhaps due to in vivo T-cell depletion of the graft resulting from sequestration of donor lymphocytes in host central lymphoid tissues.
Xun
Chang-Qing
CQ
Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109-1024, USA.
Little
Marie-Térèse
MT
Zellmer
Eustacia
E
Yu
Cong
C
Zaucha
Jan M
JM
Sale
George E
GE
Storer
Barry
B
Storb
Rainer
R
D000818:Animals; D004285:Dogs; D000068876:Fingolimod Hydrochloride; D006084:Graft Rejection; D018380:Hematopoietic Stem Cell Transplantation; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D011409:Propylene Glycols / Q000097:blood / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000276:immunology; D014916:Whole-Body Irradiation
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine