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Assessment of cellular response to mitogens in long-term allogeneic hematopoietic stem cell transplantation survivors

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Abstract

Infection is one of the major causes of death in hematopoietic stem cell transplantation (HSCT) survivors. Precise assessments of immune function after HSCT will be critical in establishing appropriate treatment and prophylaxis, such as re-vaccination. Although several surrogate markers for prediction of clinical outcomes after HSCT have been proposed, definitive markers of immune reconstitution and data on those markers in long-term survivors are lacking. In this study, cellular response to mitogens was assessed and clinical features associated with a poor response to mitogens were investigated in long-term allogeneic HSCT survivors. Age at transplantation and age at the time of mitogen stimulation test were each identified as significant risk factors for poor response to phytohemagglutinin and concanavalin A, respectively (P < 0.001 each). However, time elapsed since transplantation was not found to be correlated with responsiveness to mitogens in this study. Prospective, in-depth studies on immune reconstitution are needed to establish appropriate prophylaxis against infections after HSCT and a schedule for re-vaccination.

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Change history

  • 18 September 2021

    The original article has been updated to correct the references 10 and 11.

References

  1. Kanate AS, Majhail NS, Savani BN, Bredeson C, Champlin RE, Crawford S, et al. Indications for hematopoietic cell transplantation and immune effector cell therapy: guidelines from the American society for transplantation and cellular therapy. Biol Blood Marrow Transplant. 2020;26(7):1247–56.

    Article  CAS  Google Scholar 

  2. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143–238.

    Article  CAS  Google Scholar 

  3. Majhail NS, Tao L, Bredeson C, Davies S, Dehn J, Gajewski JL, et al. Prevalence of hematopoietic cell transplant survivors in the United States. Biol Blood Marrow Transplant. 2013;19(10):1498–501.

    Article  Google Scholar 

  4. Majhail NS, Douglas RJ. Surviving the cure: long term followup of hematopoietic cell transplant recipients. Bone Marrow Transplant. 2013;48(9):1145–51.

    Article  CAS  Google Scholar 

  5. Cordonnier C, Einarsdottir S, Cesaro S, Di Blasi R, Mikulska M, Rieger C, et al. Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis. 2019;19(6):e200–12.

    Article  Google Scholar 

  6. Ljungman P, Cordonnier C, Einsele H, Englund J, Machado CM, Storek J, et al. Vaccination of hematopoietic cell transplant recipients. Bone Marrow Transplant. 2009;44(8):521–6.

    Article  CAS  Google Scholar 

  7. Geddes M, Storek J. Immune reconstitution following hematopoietic stem-cell transplantation. Best Pract Res Clin Haematol. 2007;20(2):329–48.

    Article  CAS  Google Scholar 

  8. Fritze D, Dystant P. Detection of impaired mitogen responses in autologous whole blood of cancer patients using an optimized method of lymphocyte stimulation. Immunol Lett. 1984;8(5):243–7.

    Article  CAS  Google Scholar 

  9. Bloemena E, Roos MT, Van Heijst JL, Vossen JM, Schellekens PT. Whole-blood lymphocyte cultures. J Immunol Methods. 1989;122(2):161–7.

    Article  CAS  Google Scholar 

  10. Guideline Committee of JSHCT. Vaccinations Ver. 2. Guideline of the Japan Society for Hematopoietic Cell Transplantation, vol. 1, Osaka: Iyaku Journal; 2014. p. 162–206.

  11. Guideline Committee of JSHCT. Vaccinations Ver.3. Guideline of the Japan Society for Hematopoietic Cell Transplantation [Internet]. 2018; 1:1–50. Available from: https://www.jshct.com/uploads/files/guideline/01_05_vaccination_ver03.pdf. Accessed 20 Jul 2021.

  12. Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8.

    Article  CAS  Google Scholar 

  13. Morecki S, Gelfand Y, Nagler A, Or R, Naparstek E, Varadi G, et al. Immune reconstitution following allogeneic stem cell transplantation in recipients conditioned by low intensity vs myeloablative regimen. Bone Marrow Transplant. 2001;28(3):243–9.

    Article  CAS  Google Scholar 

  14. Yong MK, Cameron PU, Slavin MA, Cheng AC, Morrissey CO, Bergin K, et al. Low T-cell responses to mitogen stimulation predicts poor survival in recipients of allogeneic hematopoietic stem cell transplantation. Front Immunol. 2017;8:1506.

    Article  Google Scholar 

  15. Shiobara S, Ueda M, Harada M, Mori T, Matsue K, Nakao S, et al. Long-term observation of immunologic reconstitution after allogeneic bone marrow transplantation: differences in recovery among functional T cell subsets. Nihon Ketsueki Gakkai Zasshi. 1989;52(1):55–62.

    CAS  PubMed  Google Scholar 

  16. Soiffer RJ, Bosserman L, Murray C, Cochran K, Daley J, Ritz J. Reconstitution of T-cell function after CD6-depleted allogeneic bone marrow transplantation. Blood. 1990;75(10):2076–84.

    Article  CAS  Google Scholar 

  17. Israeli M, Klein T, Herscovici C, Ram R, Shpilberg O, Sredni B, et al. Cellular immune function monitoring after allogeneic haematopoietic cell transplantation: evaluation of a new assay. Clin Exp Immunol. 2013;172(3):475–82.

    Article  CAS  Google Scholar 

  18. Jo Y, Lim J, Kim Y, Han K, Min W-S, Oh E-J. CD4 T-cell function assay using Cylex ImmuKnow and lymphocyte subset recovery following allogeneic hematopoietic stem cell transplantation. Transpl Immunol. 2015;33(2):78–83.

    Article  CAS  Google Scholar 

  19. Gesundheit B, Budowski E, Israeli M, Shapira MY, Resnick IB, Bringer R, et al. Assessment of CD4 T-lymphocyte reactivity by the Cylex ImmuKnow assay in patients following allogeneic hematopoietic SCT. Bone Marrow Transplant. 2010;45(3):527–33.

    Article  CAS  Google Scholar 

  20. Hicks MJ, Jones JF, Thies AC, Weigle KA, Minnich LL. Age-related changes in mitogen-induced lymphocyte function from birth to old age. Am J Clin Pathol. 1983;80(2):159–63.

    Article  CAS  Google Scholar 

  21. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015;15(8):486–99.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank all the participants of this study.

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Authors and Affiliations

  1. Department of Hematology, Japanese Red Cross Nagoya First Hospital, 3-35, Michishita-cho, Nakamura-ku, Nagoya, Aichi, Japan

    Takahiko Sato, Miyo Goto, Marie Ohbiki, Tatsunori Goto, Takanobu Morishita, Aika Seto, Yukiyasu Ozawa & Koichi Miyamura

  2. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Takahiko Sato

Authors
  1. Takahiko Sato
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  2. Miyo Goto
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  3. Marie Ohbiki
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  7. Yukiyasu Ozawa
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Contributions

TS and KM contributed to the conception and design of the study; TS collected and analyzed the data; TS wrote the manuscript, and MG, MO, TG, TM, AS, YO, KM reviewed and revised the manuscript; all authors approved the final version of the manuscript.

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Correspondence to Takahiko Sato.

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The authors declare no conflict of interest with this study.

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Sato, T., Goto, M., Ohbiki, M. et al. Assessment of cellular response to mitogens in long-term allogeneic hematopoietic stem cell transplantation survivors. Int J Hematol 114, 682–690 (2021). https://doi.org/10.1007/s12185-021-03206-7

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  • DOI: https://doi.org/10.1007/s12185-021-03206-7

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