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Conditioning Regimens

Toward a myeloablative regimen with clinical potential: II. Treosulfan induces specific skin graft tolerance across haploidentical MHC barriers

Summary:

Treosulfan is a water-soluble structural analog of busulfan, acting as a prodrug of alkylating epoxide species. It does not induce severe hepatotoxicity or veno-occlusive disease at or above the maximum tolerated dose, lacks significant nonhematological toxicity and has a limited organ toxicity. It is mainly indicated for the treatment of patients with ovarian cancer. In the present study, we report that permanent donor-specific tolerance and stable mixed multilineage chimerism can successfully be achieved across haploidentical MHC barriers when Treosulfan is administered in combination with anti-T-cell mAb and T-cell-depleted donor bone marrow cells. Furthermore, we show that less T-cell suppression is required when Treosulfan is included in the conditioning regimen. In conclusion, Treosulfan is a well-tolerated myeloablative agent with a low toxicity, and is a promising candidate drug for conditioning prior to bone marrow transplantation.

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Acknowledgements

We thank Sacco Luypen and Mathijs van Eck for assistance in the animal experiments and animal care, Joost Uittenboogaard and Wilma Witkamp for technical assistance and Wietse Kuis and Joachim Baumgart (medac) for critically reading the manuscript. This study was financially supported by the Dutch Kidney Foundation (Grant C97.1669)

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Correspondence to C J P Boog.

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van Pel, M., van Breugel, D., Vos, W. et al. Toward a myeloablative regimen with clinical potential: II. Treosulfan induces specific skin graft tolerance across haploidentical MHC barriers. Bone Marrow Transplant 33, 153–159 (2004). https://doi.org/10.1038/sj.bmt.1704333

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