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Graft-versus-host Disease

Extracorporeal photopheresis combined with pentostatin in the conditioning regimen for canine hematopoietic cell transplantation does not prevent GVHD

Bone Marrow Transplantation volume 49, pages 1198–1204 (2014)Cite this article

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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.

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Acknowledgements

We thank George Sale, MD for performing the pathology studies, Michele Spector, DVM for providing veterinary care along with the technicians in the canine facilities of the Fred Hutchinson Cancer Research Center. We also would like to thank Stacy Zellmer for DLA typing and the technicians of the hematology department for analyzing peripheral blood counts. We are also grateful for the assistance of Helen Crawford, Bonnie Larson and Sue Carbonneau in manuscript preparation. This study was supported by grants from the National Institutes of Health HL036444 and CA078902 and a grant from Therakos, Incorporated. WAB was supported by a fellowship from Deutsche Krebshilfe, Dr Mildred-Scheel-Stiftung für Krebsforschung. FRK was supported by a grant from FAPESP/Brazil and an award from the Oncology Research Faculty Development Program from the Department of Health and Human Services, NIH, Bethesda, MD.

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Author notes

  1. W A Bethge

    Present address: 4Current address: Department for Hematology and Oncology, Medical Center, University Hospital of Tuebingen, Tuebingen, Germany.,

  2. F R Kerbauy

    Present address: 5Current address: Discipline of Hematology and Hemotherapy, Universida de Federal de São Paulo, São Paulo, Brazil.,

Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA,

    W A Bethge, F R Kerbauy, E B Santos, T Gooley, R Storb & B M Sandmaier

  2. Departments of Statistics, University of Washington, Seattle, WA, USA,

    T Gooley

  3. Departments of Medicine, University of Washington, Seattle, WA, USA

    R Storb & B M Sandmaier

Authors
  1. W A Bethge
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Correspondence to B M Sandmaier.

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Bethge, W., Kerbauy, F., Santos, E. et al. Extracorporeal photopheresis combined with pentostatin in the conditioning regimen for canine hematopoietic cell transplantation does not prevent GVHD. Bone Marrow Transplant 49, 1198–1204 (2014). https://doi.org/10.1038/bmt.2014.137

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