Abstract
Rigorous T cell depletion methods can now be used to reduce the risk of graft-versus-host disease (GVHD) associated with allogeneic, hematopoietic stem cell transplantation (HSCT). However, full T cell depletion is also associated with a significant risk of graft failure. Here we hypothesize that engraftment failures after T cell-depleted HSCT may be due, in part, to the absence of GVHD prophylaxis. To test this hypothesis, we used a haploidentical mouse model to systematically measure the effects of immunosuppressive drug treatments and anti-T cell antibodies on engraftment. Results showed that engraftment was supported in all animals when hosts were pre-treated with anti-T cell antibodies, but donor chimerism was significantly improved when hosts were also treated with prednisone. Interestingly, when hosts received only pre-HSCT prednisone treatments, engraftment was not improved; when hosts received only post-HSCT prednisone (initiated near the time of irradiation), the animals became extremely ill. Results therefore demonstrated the need for both pre- and post-HSCT prednisone treatments as a means to ensure engraftment without morbidity in all host animals.
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Acknowledgements
This work was supported, in part, by Public Health Service grants P30 CA21765 and RO1 CA57419 from the National Institutes of Health, by the Assisi Foundation, and by the American Lebanese Syrian Associated Charities (ALSAC). We thank Drs Karen Slobod and Ely Benaim for useful discussions. We thank R Cross and M Paktinat for assistance with the FACScan.
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D'Costa, S., Hurwitz, J. Antibody and pre- plus post-transplant prednisone treatments support T cell-depleted stem cell engraftment without drug-induced morbidity. Bone Marrow Transplant 29, 553–556 (2002). https://doi.org/10.1038/sj.bmt.1703428
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DOI: https://doi.org/10.1038/sj.bmt.1703428