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Conditioning

Preferential depletion of host over donor T cells through in vivo decay of active rabbit-anti-thymocyte globulin levels during reduced intensity conditioning

Bone Marrow Transplantation volume 50, pages 829–833 (2015)Cite this article

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Abstract

Inadequate T-cell chimerism following reduced-intensity conditioning transplantation may contribute to graft rejection and disease relapse. Anti-thymocyte globulin (ATG) enhances early donor T-cell chimerism, but may also deplete donor T cells, increasing risks of infection and relapse. We prospectively tested administration of rabbit ATG (rATG) ⩾14 days before the infusion of the graft, followed by in vivo decay of active rATG levels, to selectively deplete host T cells. Twenty-three patients received rATG total dose 4.5 mg/kg on days −16 and −15, fludarabine 30 mg/m2 per day on day −7 through −3, IV busulfan 130 mg/m2 per day on days −4 and −3 and cyclophosphamide 1500 mg/m2 on day −2. rATG levels were therapeutic in all patients on day −14, but were sub-therapeutic (<1 μg/mL) by day 0 in 82% of patients. Median donor T-cell chimerisms on days 30 and 180 were 100% (75–100%) and 100% (90–100%), respectively. Non-relapse mortality and relapse/progression at 48 months were 17 and 30%. Cumulative incidences of acute GvHD grades II–IV and III–IV were 39 and 9%. Median follow-up is 64 months (46–79 months). Survival and disease-free survival at 48 months were 70 and 52%. These data suggest that selective depletion of host T cells using this regimen is a feasible and effective strategy.

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Acknowledgements

This research was supported by a grant from Genzyme Corporation.

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Authors and Affiliations

  1. Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA

    M Sanacore, S L Brown, K Connor, S Hilton, L E Morris, H K Holland, S R Solomon & A Bashey

  2. Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, USA

    X Zhang

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  1. M Sanacore
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  2. X Zhang
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  3. S L Brown
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  9. A Bashey
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Correspondence to A Bashey.

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This research was supported by a grant from Genzyme Corporation to assist with data management. There are no other potential conflicts of interest to declare.

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Sanacore, M., Zhang, X., Brown, S. et al. Preferential depletion of host over donor T cells through in vivo decay of active rabbit-anti-thymocyte globulin levels during reduced intensity conditioning. Bone Marrow Transplant 50, 829–833 (2015). https://doi.org/10.1038/bmt.2015.41

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