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Graft-Versus-Host Disease

Keratinocyte growth factor ameliorates acute graft-versus-host disease in a novel nonmyeloablative haploidentical transplantation model

Bone Marrow Transplantation volume 36, pages 907–915 (2005)Cite this article

Summary:

Allogeneic stem cell transplantations (SCT) are currently being used as a therapy for hematological malignancies, some solid tumors and nonmalignant bone marrow deficiencies. Nevertheless, clinical applicability is limited due to toxicity of conditioning regimens, graft-versus-host disease (GVHD) and the scarcity of HLA-identical family donors. New concepts are based on nonmyeloablative conditioning to reduce toxicity, prevention or amelioration of GVHD and the use of haploidentical donors to increase donor availability. To combine these requirements, we have developed a nonmyeloablative conditioning regimen, consisting of low-dose total body irradiation and cyclophosphamide-based chemotherapy. In a haploidentical F1 → F1 mouse model, this nonmyeloablative transplantation protocol resulted in stable full donor chimerism, but also in the development of severe GVHD. Administration of keratinocyte growth factor (KGF) reduced GVHD, evident as reduced weight loss and a lesser degree of dermatitis, compared to saline-treated controls. KGF preserved plasma citrulline and tumor necrosis factor-α levels, both indicative for reduced injury to the gastrointestinal tract. This was confirmed by histological findings. At 6 months after transplantation, survival rates were significantly higher in KGF-treated animals as compared to phosphate buffered saline-treated controls. These results indicate that KGF preserves gut integrity and might therefore contribute substantially to reduction of lethal GVHD in (nonmyeloablative) haploidentical transplantation.

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Acknowledgements

We would like to thank Mrs T Jeunhomme for performing the TNF-α ELISA's, Mr DJH Haagen for amino-acid analyses of plasma samples and Mr JPM Cleutjens for help with morphometric analyses.

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Hematology and Oncology, University Hospital Maastricht, Maastricht, The Netherlands

    A Vanclée, E B H Oving, H C Schouten & G M J Bos

  2. Department of Radiation Oncology, University of Maastricht, Maastricht, The Netherlands

    L C H W Lutgens

  3. Department of Surgery, University of Maastricht, Maastricht, The Netherlands

    N E P Deutz

  4. Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands

    M J J Gijbels

  5. Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands

    M J J Gijbels

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  1. A Vanclée
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Correspondence to A Vanclée.

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Vanclée, A., Lutgens, L., Oving, E. et al. Keratinocyte growth factor ameliorates acute graft-versus-host disease in a novel nonmyeloablative haploidentical transplantation model. Bone Marrow Transplant 36, 907–915 (2005). https://doi.org/10.1038/sj.bmt.1705157

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