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Pre-Clinical Studies

The effect of administration order of BU and CY on engraftment and toxicity in HSCT mouse model

Bone Marrow Transplantation volume 41, pages 895–904 (2008)Cite this article

Abstract

Conditioning regimens are an important issue determining the outcome of hematopoietic stem cell transplantation (HSCT). Less toxicity, early engraftment and no relapse are the aims of efficient conditioning. Our objective was to investigate the long-term effects of BU–CY and their administration order on the toxicity and chimerism in a mouse model of HSCT. Female BALB/c mice were treated with either BU (15 mg/kg/day × 4)–CY (100 mg/kg/day × 2) or CY–BU. Treated mice were transplanted with Sca-1+ cells from male BALB/c mice. Until 90 days after HSCT, the animals were monitored for body weight and analyzed for cellular phenotype of the thymus, spleen and BM, total chimerism, the spleen chimerism of DCs and T regulatory (Treg) cells, and hepatotoxicity. BU–CY and CY–BU treatments exerted comparable myeloablative and immunosuppressive effects. The long-term engraftment of donor cells in the BM and thymus regeneration showed the same features in both groups. However, the two regimens differed; in general, hepatotoxicity and chimerism of DC and Treg cells. In the long term, BU–CY, but not CY–BU caused a marked decrease in body weight and a significant increase in the activities of the liver enzymes, particularly aspartate amino transferase (AST). We conclude that the alteration of the administration order of BU–CY to CY–BU not only gives the same level of engraftment but also reduces the toxicity of the conditioning regimen that might be valuable specially in young patients who are undergoing HSCT.

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Acknowledgements

This study was supported by grants from the Swedish Cancer Foundation and the Swedish Children Cancer Society.

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Author notes

  1. B Sadeghi and M Jansson: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Laboratory Medicine, Experimental Cancer Medicine, Karolinska Institutet and Clinical Research Center Novum, Karolinska University Hospital—Huddinge, Stockholm, Sweden

    B Sadeghi, M Jansson, Z Hassan & M Hassan

  2. Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital—Huddinge, Stockholm, Sweden

    Z Hassan

  3. Division of Obstetrics and Gynecology, Karolinska University Hospital—Huddinge, Stockholm, Sweden

    M Mints

  4. Division of Hematology, Karolinska University Hospital—Huddinge, Stockholm, Sweden

    H Hägglund

  5. Department of Biochemistry and Biophysics, Arrhenius Laboratories for the Natural Sciences, Stockholm University, Stockholm, Sweden

    M Abedi-Valugerdi

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  1. B Sadeghi
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Correspondence to M Hassan.

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Sadeghi, B., Jansson, M., Hassan, Z. et al. The effect of administration order of BU and CY on engraftment and toxicity in HSCT mouse model. Bone Marrow Transplant 41, 895–904 (2008). https://doi.org/10.1038/sj.bmt.1705996

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