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Baseline immune dysregulation in autologous stem cell transplant recipients is associated with a ‘graft versus host’-like syndrome and poor outcomes

Bone Marrow Transplantation volume 55, pages 1879–1881 (2020)Cite this article

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The development of graft versus host disease (GVHD) after allogeneic transplantation represents a major cause for morbidity and mortality [1] and results from the recognition of recipient antigens by donor T and natural killer (NK) lymphocytes [2]. The development of clinical and histopathological changes similar to GVHD following autologous stem cell transplant (ASCT) is a rare and poorly understood phenomenon [3] and is referred to as autologous GVHD. Autologous GVHD was defined as the development of clinical and histo-pathological findings indicative of GVHD in ASCT recipients, as determined by pathology review. This syndrome is characterized by the development of acute onset diarrhea, skin rash, and occasionally elevated liver enzymes and has been described in few case series in the literature [4, 5]. It is controversial as to whether this syndrome exists and whether its development adversely affects post-transplant outcomes [3].

The mechanisms for the development of autologous GVHD are distinctly different from GVHD since no allogeneic cells are introduced into the host. It has been postulated that the use of immunomodulatory agents prior to transplantation could trigger its development. Given the lack of understanding of the pathophysiology of autologous GVHD and the controversies in reported outcomes, we aimed to (1) analyze outcomes, clinical and histopathological correlatives for the development of autologous GVHD in ASCT recipients and (2) determine baseline T- and NK-cell functions in patients who developed GVHD after ASCT compared with matched controls.

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Fig. 1: Baseline characteristics and clinical outcomes of all 19 patients included in our study.

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Acknowledgements

The study was partially supported by NCI K12 CA090628 (SSK), NCCN Young Investigator Award (S.S.K), the Predolin Foundation, and the Mayo Clinic Center for Individualized Medicine (SSK). TA has received funding from ASH RTAF, Mayo Clinic/Iowa Lymphoma SPORE, and the Mayo Clinic Division of Hematology.

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Authors and Affiliations

  1. Department of Medicine, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Theodora Anagnostou

  2. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    Reona Sakemura, Cynthia L. Forsman, Mrinal S. Patnaik, Jonas Paludo, Dennis A. Gastineau, Francis K. Buadi, Luis F. Porrata, Shaji K. Kumar, Morie A. Gertz, Matha Q. Lacy, Angela Dispenzieri, Wilson I. Gonsalves, William J. Hogan, Shahrukh K. Hashmi, Hassan Alkhateeb, Mithun V. Shah, Mark R. Litzow & Saad S. Kenderian

  3. Department of Dermatology, Mayo Clinic, Rochester, MN, USA

    Julia S. Lehman

  4. Department of Immunology, Mayo Clinic, Rochester, MN, USA

    Saad S. Kenderian

  5. Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA

    Saad S. Kenderian

Authors
  1. Theodora Anagnostou
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  2. Reona Sakemura
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  6. Dennis A. Gastineau
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  7. Francis K. Buadi
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  8. Luis F. Porrata
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  9. Shaji K. Kumar
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  11. Matha Q. Lacy
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  12. Angela Dispenzieri
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  13. Wilson I. Gonsalves
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  15. William J. Hogan
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  16. Shahrukh K. Hashmi
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  17. Hassan Alkhateeb
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  18. Mithun V. Shah
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  19. Mark R. Litzow
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  20. Saad S. Kenderian
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Contributions

TA and SSK designed the study and wrote the manuscript. TA, SSK, RS, and CF performed experiments. All authors were involved in manuscript preparation and approved the final version.

Corresponding author

Correspondence to Saad S. Kenderian.

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Conflict of interest

SSK is an inventor on patents in the field of CAR-T cell immunotherapy that are licensed to Novartis, Humanigen and Mettaforge. SSK receives research funding from Kite, Gilead, Juno, Celegene, Novartis, Humanigen, Tolero, Sunesis, Lentigen, and Morphosys. SSK serves on advisory boards for Kite, and Humanigen. These disclosures are not directly related to this work. The rest of the authors report no financial disclosures.

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Anagnostou, T., Sakemura, R., Forsman, C.L. et al. Baseline immune dysregulation in autologous stem cell transplant recipients is associated with a ‘graft versus host’-like syndrome and poor outcomes. Bone Marrow Transplant 55, 1879–1881 (2020). https://doi.org/10.1038/s41409-020-0851-3

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  • DOI: https://doi.org/10.1038/s41409-020-0851-3

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