title: Extracorporeal photopheresis in addition to pentostatin in conditioning for canine hematopoietic cell transplantation: role in engraftment.
abstract: Extracorporeal photopheresis (ECP) and the purine analog pentostatin exert potent immunomodulatory effects, but have not been evaluated for their ability to enhance engraftment of hematopoietic stem cells. We evaluated, in a canine model of dog leukocyte antigen (DLA)-identical hematopoietic cell transplantation (HCT), whether ECP in combination with pentostatin could enhance engraftment using a nonmyeloablative regimen consisting of 100 cGy TBI and postgrafting immunosuppression with mycophenolate mofetil and CYA. We have shown previously that with 100 cGy TBI alone as conditioning, all of the six dogs rejected their grafts 2-12 weeks after HCT. With the addition of pentostatin to 100 cGy TBI, 6 of 10 dogs rejected their graft. We now tested the additional use of ECP alone (n=2) or ECP and 3-6 doses of pentostatin (n=7) before 100 cGy TBI and HCT. Eight out of nine dogs rejected their grafts within 6-11 weeks after HCT. Compared with data without ECP, we failed to demonstrate a positive impact of the use of either ECP or pentostatin for prevention of rejection.
authors.affiliation: Clinical Research Division, Transplantation Biology Program, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109-1024, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: Bethge
authors.forename: F R
authors.initials: FR
authors.lastname: Kerbauy
authors.forename: E
authors.initials: E
authors.lastname: Santos
authors.forename: T A
authors.initials: TA
authors.lastname: Gooley
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.forename: B M
authors.initials: BM
authors.lastname: Sandmaier
mesh_terms: D000818:Animals; D004285:Dogs; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006649:Histocompatibility Antigens / Q000276:immunology; D056747:Immunomodulation; D015649:Pentostatin / Q000494:pharmacology*; D017893:Photopheresis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous
chemical_list: D006649:Histocompatibility Antigens; D015649:Pentostatin