title: Extracorporeal photopheresis combined with pentostatin in the conditioning regimen for canine hematopoietic cell transplantation does not prevent GVHD.
abstract: Extracorporeal photopheresis (ECP) and the purine analog pentostatin exert potent immunomodulatory effects. We evaluated the use of these treatment modalities to prevent GVHD in a canine model of unrelated dog leukocyte Ag-mismatched hematopoietic cell transplantation, after conditioning with 920 cGy TBI. We have shown previously in this model that 36/40 dogs given MTX alone as postgrafting immunosuppression engrafted and that 25 of 40 dogs had severe GVHD and median survival of 21 days. In the current study, nine dogs received conditioning with 920 cGy TBI and postgrafting MTX either with ECP on days -2 to -1 alone (n=5) or ECP on days -6 and -5 combined with two doses of pentostatin (days -4 to -3) (n=4). Seven of nine dogs achieved engraftment. Six dogs developed severe acute GVHD (four in the group with ECP alone and two with pentostatin and ECP). We failed to demonstrate a positive impact of ECP and pentostatin for the prevention of GVHD compared with historical control dogs.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: Bethge
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: F R
authors.initials: FR
authors.lastname: Kerbauy
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Santos
authors.affiliation: 1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA [2] Departments of Statistics, University of Washington, Seattle, WA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Gooley
authors.affiliation: 1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA [2] Departments of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.affiliation: 1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA [2] Departments of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Sandmaier
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004283:Dog Diseases / Q000517:prevention & control / Q000628:therapy*; D004285:Dogs; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000517:prevention & control / Q000662:veterinary*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D015649:Pentostatin / Q000494:pharmacology*; D017893:Photopheresis / Q000379:methods / Q000662:veterinary*; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D015649:Pentostatin