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Effect of plasmapheresis on ATG (Thymoglobulin) clearance prior to adoptive T cell transfer

Bone Marrow Transplantation volume 54, pages 2110–2116 (2019)Cite this article

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Abstract

The effect of anti-thymocyte globulin (ATG) on the outcome of hematopoietic stem cell transplantation (SCT) is dependent on formulation, dose and exposure. However, ATG levels are not routinely measured and therapeutic levels are not well defined. In ex vivo T cell-deplete SCT, the potential effect of residual ATG has important implications on the timing of adoptive T cell transfer. Here we measured active rabbit ATG concentration using a flow cytometry-based method that can be implemented in any laboratory. Three adult patients received 6 mg/kg Thymoglobulin over 4 days, leading to peak plasma active ATG concentration of 20.8 ± 1.4 µg/mL, suggesting volume of distribution of 16–19 L. The half-life of active ATG was 6.1 ± 0.7 days and plasmapheresis at Day 25 ± 1 post-transplant reduced mean plasma concentration from 1.25 to 0.61 µg/mL. Total ATG and active ATG do not have a constant relationship because of differences in volumes of distribution and half-lives. Thymoglobulin can mediate antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro at concentrations as low as 0.03 µg/mL, with a log-linear relationship between ATG concentration and ADCC. Plasmapheresis can remove ATG but likely has modest biological impact when performed 4 weeks after 6 mg/kg ATG.

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Acknowledgements

This study was supported by a Project Grant (APP1053135) from the National Health and Medical Research Council (NH&MRC, Australia), QIMR Berghofer Ride To Conquer Cancer Flagship Award and Royal Brisbane, and Women’s Hospital Foundation. S-KT was supported by an NH&MRC Early Career Fellowship (APP1054786) and GRH was supported by a QLD Health Senior Clinical Research Fellowship.

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Authors and Affiliations

  1. QIMR Berghofer Medical Research Institute, Herston, QLD, Australia

    Ping Zhang, Geoffrey R. Hill & Siok-Keen Tey

  2. Department of Haematology and Bone Marrow Transplantation, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia

    Cameron I. Curley, Kari Mudie, Midori Nakagaki, Geoffrey R. Hill & Siok-Keen Tey

  3. Department of Pharmacy, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia

    Midori Nakagaki & Jason A. Roberts

  4. University of Queensland Centre for Clinical Research, Faculty of Medicine, University of Queensland, Herston, QLD, Australia

    Jason A. Roberts

  5. Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia

    Jason A. Roberts

  6. Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, University of Queensland, Herston, QLD, Australia

    Jason A. Roberts

  7. School of Clinical Medicine – Royal Brisbane Clinical Unit, Faculty of Medicine, University of Queensland, Herston, QLD, Australia

    Siok-Keen Tey

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Zhang, P., Curley, C.I., Mudie, K. et al. Effect of plasmapheresis on ATG (Thymoglobulin) clearance prior to adoptive T cell transfer. Bone Marrow Transplant 54, 2110–2116 (2019). https://doi.org/10.1038/s41409-019-0505-5

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