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Chronic liver graft-versus-host disease in allogeneic hematopoietic stem cell transplantation recipients during tapering or after stopping calcineurin inhibitors

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Abstract

Chronic graft-versus-host disease (cGVHD) of the liver is often observed in allogeneic hematopoietic stem cell transplantation (allo-HSCT) during tapering or after stopping calcineurin inhibitors (CI). We conducted a retrospective analysis of 242 allo-HSCT recipients whose CI dose was reduced to less than 40 mg of cyclosporin A or 0.4 mg of tacrolimus to clarify the clinical characteristics of liver GVHD in patients on low-dose CI. Sixty patients (25%) developed clinically suspected liver cGVHD while on low-dose CI. Multivariate analysis showed that donor age ≥ 40 years [hazard ratio (HR) 2.20], myeloablative conditioning (HR 2.19), female donor to male recipient (HR 2.53) and recipient seropositivity for herpes simplex virus (HR 2.52) were significant risk factors for liver cGVHD during low-dose CI period. Peak aspartate aminotransferase and alanine aminotransferase levels were higher in patients with liver GVHD during low-dose CI period than in other periods. Twenty-seven patients were initially treated with resumption of CI or a CI dose increase and 21 responded. Among the 18 patients treated with corticosteroids, total bilirubin was a risk factor for failure of corticosteroid therapy. The results of this study clarified the clinical characteristics of liver GVHD in patients on low-dose CIs.

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References

  1. Arai S, Arora M, Wang T, Spellman SR, He W, Couriel DR, et al. Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Tr. 2015;21:266–74.

    Article  Google Scholar 

  2. Grube M, Holler E, Weber D, Holler B, Herr W, Wolff D. Risk Factors and outcome of chronic graft-versus-host disease after allogeneic stem cell transplantation—results from a single-center observational study. Biol Blood Marrow Transplant. 2016;22:1781–91.

    Article  Google Scholar 

  3. Lee SJ, Klein JP, Barrett AJ, Ringden O, Antin JH, Cahn J-Y, et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood. 2002;100:406–14.

    Article  CAS  Google Scholar 

  4. Jagasia MH, Greinix HT, 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 Transplant. 2015;21:389–401.

    Article  Google Scholar 

  5. Koyama D, Ito M, Yokohata E, Watakabe K, Onodera K, Goto T, et al. Autoimmune-like hepatitis after allogeneic hematopoietic stem cell transplantation: humoral hepatic GvHD. Bone Marrow Transplant. 2017;52:151–3.

    Article  CAS  Google Scholar 

  6. Sullivan KM, Shulman HM, Storb R, Weiden PL, Witherspoon RP, McDonald GB, et al. Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood. 1981;57:267–76.

    Article  CAS  Google Scholar 

  7. Chen C-T, Liu C-Y, Yu Y-B, Liu C-J, Hsiao L-T, Gau J-P, et al. Characteristics and risk of chronic graft-versus-host disease of liver in allogeneic hematopoietic stem cell transplant recipients. PLoS ONE. 2017;12:e0185210.

    Article  Google Scholar 

  8. Greinix HT, Loddenkemper C, Pavletic SZ, Holler E, Socié G, Lawitschka A, et al. Diagnosis and staging of chronic graft-versus-host disease in the clinical practice. Biol Blood Marrow Transplant. 2011;17:167–75.

    Article  Google Scholar 

  9. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452.

    Article  CAS  Google Scholar 

  10. Flowers MED, Inamoto Y, Carpenter PA, Lee SJ, Kiem H-P, Petersdorf EW, et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 2011;117:3214–9.

    Article  CAS  Google Scholar 

  11. Kondo M, Kojima S, Horibe K, Kato K, Matsuyama T. Risk factors for chronic graft-versus-host disease after allogeneic stem cell transplantation in children. Bone Marrow Transplant. 2001;27:727.

    Article  CAS  Google Scholar 

  12. Kanda J, Nakasone H, Atsuta Y, Toubai T, Yokoyama H, Fukuda T, et al. Risk factors and organ involvement of chronic GVHD in Japan. Bone Marrow Transplant. 2014;49:228.

    Article  CAS  Google Scholar 

  13. Kollman C, Howe CWS, Anasetti C, Antin JH, Davies SM, Filipovich AH, et al. Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood. 2001;98:2043–51.

    Article  CAS  Google Scholar 

  14. Boström L, Ringdén O, Jacobsen N, Zwaan F, Nilsson BO. A European multicenter study of chronic graft-versus-host disease. Transplantation. 1990;49:1100–4.

    Article  Google Scholar 

  15. Boström L, Ringdén O, Sundberg B, Ljungman P, Linde A, Nilsson B. Pretransplant herpes virus serology and chronic graft-versus-host disease. Bone Marrow Transplant. 1989;4:547–52.

    PubMed  Google Scholar 

  16. Atsuta Y, Suzuki R, Yamamoto K, Terakura S, Iida H, Kohno A, et al. Risk and prognostic factors for Japanese patients with chronic graft-versus-host disease after bone marrow transplantation. Bone Marrow Transplant. 2006;37:289.

    Article  CAS  Google Scholar 

  17. Loeb KR, Woolston DW, Shulman HM. The pathological spectrum of hepatic GVHD. In: Yeung CS, Shulman HM, editors. Pathology of graft vs host disease, a case based teaching guide. Switzerland: Springer Nature; 2019. p. 169–83.

    Chapter  Google Scholar 

  18. Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 1999;31:929–38.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank all of the clinicians at our center who helped to obtain data for this study.

Funding

We report no financial support relevant to this study.

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Authors and Affiliations

  1. Division of Hematology, Jichi Medical University Saitama Medical Center, 1-847 Amanuma, Omiya-ku, Saitama, Saitama, 330-8503, Japan

    Kazuki Yoshimura, Shun-ichi Kimura, Masakatsu Kawamura, Shunto Kawamura, Junko Takeshita, Nozomu Yoshino, Yukiko Misaki, Ayumi Gomyo, Shimpei Matsumi, Yu Akahoshi, Masaharu Tamaki, Machiko Kusuda, Kazuaki Kameda, Hidenori Wada, Koji Kawamura, Miki Sato, Kiriko Terasako-Saito, Aki Tanihara, Hideki Nakasone, Shinichi Kako & Yoshinobu Kanda

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  1. Kazuki Yoshimura
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  2. Shun-ichi Kimura
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  15. Koji Kawamura
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  16. Miki Sato
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  18. Aki Tanihara
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  19. Hideki Nakasone
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  20. Shinichi Kako
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  21. Yoshinobu Kanda
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Contributions

KY, S-IK and YK conceived the original idea. KY collected the data. KY and S-IK performed statistical analysis. KY, S-IK and YK analysed results and interpreted the data. KY wrote the manuscript. The other authors contributed to critical revision of the manuscript. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Yoshinobu Kanda.

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Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

This retrospective study was approved by the Institutional Review Board of Jichi Medical University Saitama Medical Center and performed in accordance with the Declaration of Helsinki and its later amendments.

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Cite this article

Yoshimura, K., Kimura, Si., Kawamura, M. et al. Chronic liver graft-versus-host disease in allogeneic hematopoietic stem cell transplantation recipients during tapering or after stopping calcineurin inhibitors. Int J Hematol 114, 674–681 (2021). https://doi.org/10.1007/s12185-021-03202-x

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  • DOI: https://doi.org/10.1007/s12185-021-03202-x

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