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Clinical and immunologic responses to extracorporeal photopheresis and low-dose IL-2 in patients with steroid refractory chronic graft-versus host disease

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Fig. 1: Treatment plan, baseline organ involvement and NIH severity of enrolled patients and the clinical outcomes.

Data availability

The data supporting the findings of the study are available on request from the corresponding author (AS; asalhotra@coh.org). The data are not publicly available due to their containing information that could compromise the privacy of research participants

References

  1. Thornton AM, Shevach EM. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med. 1998;188:287–96. https://doi.org/10.1084/jem.188.2.287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zorn E, Kim HT, Lee SJ, Floyd BH, Litsa D, Arumugarajah S, et al. Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease. Blood. 2005;106:2903–11. https://doi.org/10.1182/blood-2005-03-1257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chinen T, Kannan AK, Levine AG, Fan X, Klein U, Zheng Y, et al. An essential role for the IL-2 receptor in T(reg) cell function. Nat Immunol. 2016;17:1322–33. https://doi.org/10.1038/ni.3540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Matsuoka K, Koreth J, Kim HT, Bascug G, McDonough S, Kawano Y, et al. Low-dose interleukin-2 therapy restores regulatory T cell homeostasis in patients with chronic graft-versus-host disease. Sci Transl Med. 2013;5:179ra143 https://doi.org/10.1126/scitranslmed.3005265

    Article  CAS  Google Scholar 

  5. Ito S, Bollard KM, Carlsten M, Malenhorst JJ, Biancotto A, Wang E, et al. Ultra-low dose interleukin-2 promotes immune-modulating function of regulatory T cells and natural killer cells in healthy volunteers. Mol Ther. 2014;22:1388–95. https://doi.org/10.1038/mt.2014.50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea EP, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. N. Engl J Med. 2011;365:2055–66. https://doi.org/10.1056/NEJMoa1108188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Foss FM, Gorgun G, Miller KB. Extracorporeal photopheresis in chronic graft-versus-host disease. Bone Marrow Transpl. 2002;29:719–25. https://doi.org/10.1038/sj.bmt.1703529

    Article  CAS  Google Scholar 

  8. Inamoto Y, Flowers MED, Sandmaier BM, Aki SZ, Carpenter PA, Lee SJ, et al. Failure-free survival after initial systemic treatment of chronic graft-versus-host disease. Blood. 2014;124:1363–71. https://doi.org/10.1182/blood-2014-03-563544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Jagasia MH, Hildegard GT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. the 2014 diagnosis and staging working group report. Biol Blood Marrow Transpl. 2015;21:389–401.e381. https://doi.org/10.1016/j.bbmt.2014.12.001

    Article  Google Scholar 

  10. Couriel DR, Hosing C, Saliba R, Shpall EJ, Anderlini P, Rhodes B, et al. Extracorporeal photochemotherapy for the treatment of steroid-resistant chronic GVHD. Blood. 2006;107:3074–80. https://doi.org/10.1182/blood-2005-09-3907

    Article  CAS  PubMed  Google Scholar 

  11. Koreth J, Kim HT, Jones KT, Lange PB, Reynolds CG, Chammas MJ, et al. Efficacy, durability, and response predictors of low-dose interleukin-2 therapy for chronic graft-versus-host disease. Blood. 2016;128:130–7. https://doi.org/10.1182/blood-2016-02-702852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Belizaire R, Kim HT, Poryanda SJ, Mircovic NV, Hipolito E, Savage WJ, et al. Efficacy and immunologic effects of extracorporeal photopheresis plus interleukin-2 in chronic graft-versus-host disease. Blood Adv. 2019;3:969–79. https://doi.org/10.1182/bloodadvances.2018029124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

IL-2 used in this trial was generously provided by Prometheus labs. Authors would like to thank City of Hope staff and nurses, as well as the patients and their families, without whom this work would not be possible. We would like to thank Ms. Golnaz Namdar (CRC) and Ms. Maridel Blandino (CRN) for their hard work.

Funding

This Phase 2 trial was funded by intramural Chairs Discretionary grant and NIH P30 CA033572 (Biostatistics and Genomics Core).

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Contributions

AS and RN designed and conducted the study.SM helped write the paper. MT helped with statistical analysis. XW, WT and HQ performed the corelative studies. MAM, IA, BM, EK, ES and AP helped with patient care.

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Correspondence to Amandeep Salhotra.

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The authors declare no competing interests.

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Salhotra, A., Talley, M., Wu, X. et al. Clinical and immunologic responses to extracorporeal photopheresis and low-dose IL-2 in patients with steroid refractory chronic graft-versus host disease. Bone Marrow Transplant 57, 1045–1047 (2022). https://doi.org/10.1038/s41409-022-01671-0

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