Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Split dose ATG strategy prevents grade III-IV acute GVHD and is associated with immune surrogates of GVL

Bone Marrow Transplantation volume 57, pages 1629–1631 (2022)Cite this article

Subjects

Highlights

Our split dose ATG strategy resulted in complete prevention of grade III-IV aGVHD, relatively low cGVHD, NRM, and high GRFS. It was associated with enhanced immune reconstitution, and relapse predictive phenotypes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Clinical and immune phenotypic outcomes associated with split dose ATG.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Arai Y, Jo T, Matsui H, Kondo T, Takaori-Kondo A. Efficacy of antithymocyte globulin for allogeneic hematopoietic cell transplantation: a systematic review and meta-analysis. Leuk Lymphoma. 2017;58:1840–8.

    Article  CAS  Google Scholar 

  2. Bosch M, Dhadda M, Hoegh-Petersen M, Liu Y, Hagel L, Podgorny P, et al. Immune reconstitution after anti-thymocyte globulin-conditioned hematopoietic cell transplantation. Cytotherapy. 2012;14:1258–75.

    Article  CAS  Google Scholar 

  3. Soiffer RJ, Lerademacher J, Ho V, Kan F, Artz A, Champlin RE, et al. Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Blood. 2011;117:6963–70.

    Article  CAS  Google Scholar 

  4. Divito SJ, Aasebø AT, Matos TR, Hsieh PC, Collin M, Elco CP, et al. Peripheral host T cells survive hematopoietic stem cell transplantation and promote graft-versus-host disease. J Clin Invest. 2020;130:4624–36.

    Article  CAS  Google Scholar 

  5. Li N, Chen Y, He W, Yi T, Zhao D, Zhang C, et al. Anti-CD3 preconditioning separates GVL from GVHD via modulating host dendritic cell and donor T-cell migration in recipients conditioned with TBI. Blood. 2009;113:953–62.

    Article  CAS  Google Scholar 

  6. Gul Z, Van Meter E, Abidi M, Ditah I, Abdul-Hussein M, Deol A, et al. Low blood lymphocyte count at 30 days post transplant predicts worse acute GVHD and survival but not relapse in a large retrospective cohort. Bone Marrow Transpl. 2015;50:432–7.

    Article  CAS  Google Scholar 

  7. Thoma MD, Huneke TJ, DeCook LJ, Johnson ND, Wiegand RA, Litzow MR, et al. Peripheral blood lymphocyte and monocyte recovery and survival in acute leukemia postmyeloablative allogeneic hematopoietic stem cell transplant. Biol Blood Marrow Transpl. 2012;18:600–7.

    Article  Google Scholar 

  8. Admiraal R, van Kesteren C, Jol-van der Zijde CM, Lankester AC, Bierings MB, Egberts TC, et al. Association between anti-thymocyte globulin exposure and CD4+ immune reconstitution in paediatric haemopoietic cell transplantation: a multicentre, retrospective pharmacodynamic cohort analysis. Lancet Haematol. 2015;2:e194–203.

    Article  Google Scholar 

  9. Ranti J, Kurki S, Salmenniemi U, Putkonen M, Salomäki S, Itälä-Remes M. Early CD8+-recovery independently predicts low probability of disease relapse but also associates with severe GVHD after allogeneic HSCT. PLoS One. 2018;13:e0204136.

    Article  Google Scholar 

  10. Minculescu L, Marquart HV, Friis LS, Petersen SL, Schiødt I, Ryder LP, et al. Early Natural Killer Cell Reconstitution Predicts Overall Survival in T Cell-Replete Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transpl. 2016;22:2187–93.

    Article  CAS  Google Scholar 

  11. Admiraal R, Nierkens S, Bierings MB, Bredius RGM, van Vliet I, Jiang Y, et al. Individualised dosing of anti-thymocyte globulin in paediatric unrelated allogeneic haematopoietic stem-cell transplantation (PARACHUTE): a single-arm, phase 2 clinical trial. Lancet Haematol. 2022;9:e111–20.

    Article  Google Scholar 

Download references

Acknowledgements

This research is supported with funds from The University of Nebraska Foundation. Presented in abstract form at the 57th European bone marrow transplant meeting, Prague, Czech March 2022.

Author information

Authors and Affiliations

  1. Division of Hematology & Oncology, University of Nebraska Medical Center, Omaha, NE, USA

    Zaid Al-Kadhimi, Lori Maness-Harris, Vijaya Raj Bhatt, Krishna Gundabolu, Matthew Lunning, Gregory Bociek, Christopher D’Angelo, Avyakta Kallam, James Armitage, Khansa Abdullah, Angela Hunter, Sarah Mccaslin, Michael Callahan II & Julie Vose

  2. Department of Pathology & Microbiology, University of Nebraska Medical Center, Omaha, NE, USA

    Samuel Pirruccello, Kathryn Cole, Steven Hinrichs & James Talmadge

  3. Division of Hematology/Oncology, Aurora Health Care, Milwaukee, WI, USA

    Zartash Gul

  4. Department of Laboratory Medicine & Pathology, Mayo Clinic, Rochester, NY, USA

    Jane Yuan

  5. Division of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA

    Elizabeth Lyden & Lynnette Smith

Authors
  1. Zaid Al-Kadhimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samuel Pirruccello
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zartash Gul
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lori Maness-Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vijaya Raj Bhatt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Krishna Gundabolu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jane Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Matthew Lunning
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gregory Bociek
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Christopher D’Angelo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Avyakta Kallam
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. James Armitage
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Khansa Abdullah
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Angela Hunter
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Sarah Mccaslin
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Elizabeth Lyden
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Lynnette Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Michael Callahan II
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Kathryn Cole
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Steven Hinrichs
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. James Talmadge
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Julie Vose
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ZA, JT, and SH designed the study; SP and JY designed, executed, and analyzed flow cytometry data; ZG collected data and analyzed disease risk for relapse: KA, AH and SM collected and analyzed data; LM, KG and VRB analyzed data and adjudicated GVHD type and grading: EL and LS performed the statistical analysis of clinical outcomes and relapse immune correlates; MC performed statistical analysis of immune reconstitution phenotypes compared with healthy controls; ML, GB, CD, AK, JA, and JV analyzed clinical and immunologic data; and all authors wrote, reviewed, and approved the final version of the manuscript.

Corresponding author

Correspondence to Zaid Al-Kadhimi.

Ethics declarations

Competing interests

VRB reports participating in Safety Monitoring Committee for Protagonist, and receiving consulting fees from Genentech, Incyte, Servier Pharmaceuticals LLC, and Abbvie, research funding (institutional) from Abbvie, Pfizer, Incyte, Jazz, and National Marrow Donor Program, and drug support (institutional) from Oncoceutics for a trial. KG consulting: Bayer consumer care, CTI biopharma, BMS, Blueprint Medicines, Jazz Pharmaceuticals, BioMarin Pharmaceuticals. Institutional funding: Samus therapeutics, Incyte, Pfizer, Autolus therapeutics. JV Consulting: Morphosys, Abbvie, Janssen, Astra-Zeneca, MEI Pharma, Daiichi Sankyo, Johnson and Johnson, Pharmacyclics, Genentech. Research: Loxo Pharma, Novartis, Kite.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Al-Kadhimi, Z., Pirruccello, S., Gul, Z. et al. Split dose ATG strategy prevents grade III-IV acute GVHD and is associated with immune surrogates of GVL. Bone Marrow Transplant 57, 1629–1631 (2022). https://doi.org/10.1038/s41409-022-01772-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-022-01772-w

This article is cited by

Search

Advanced search

Quick links