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Pre-Clinical Studies

Extracorporeal photopheresis in addition to pentostatin in conditioning for canine hematopoietic cell transplantation: role in engraftment

Bone Marrow Transplantation volume 46, pages 1382–1388 (2011)Cite this article

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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.

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Acknowledgements

We thank Michele Spector, DVM for providing veterinary care along with the investigators who participated in the weekend treatments and the technicians in the canine facilities of the Fred Hutchinson Cancer Research Center. We are grateful to Roche for kindly providing MMF. We also thank Stacy Zellmer for coordination of dog use and DLA-typing. We are also grateful for the assistance of Helen Crawford, Bonnie Larson and Sue Carbonneau in manuscript preparation. We are grateful for research funding from the National Institutes of Health, Bethesda, MD Grants P01HL036444, P01CA078902 and P30CA015704. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or its subsidiary Institutes and Centers. In addition, this work was supported by a grant from Therakos Incorporated and Supergen 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 of Hematology and Oncology, Medical Center, University Hospital of Tuebingen, Germany.,

  2. F R Kerbauy

    Present address: 5Current address: Discipline of Hematology and Hemotherapy-Universidade Federal de São Paulo, UNIFESP/EPM, Brazil.,

Authors and Affiliations

  1. Clinical Research Division, Transplantation Biology Program, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA

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

  2. Department of Biostatistics, University of Washington, Seattle, WA, USA

    T A Gooley

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

    R Storb & B M Sandmaier

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  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 in addition to pentostatin in conditioning for canine hematopoietic cell transplantation: role in engraftment. Bone Marrow Transplant 46, 1382–1388 (2011). https://doi.org/10.1038/bmt.2010.301

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