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:

Impact of standard-dose dipeptidyl peptidase-4 inhibitors on the incidence of graft-versus-host disease after allogeneic hematopoietic cell transplantation

Bone Marrow Transplantation volume 58, pages 452–455 (2023)Cite this article

Subjects

The prophylactic administration of high-dose sitagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor that have been originally used for the treatment of diabetes mellitus, was reportedly associated with a low incidence of acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) [1]. DPP-4 is expressed on T lymphocytes and has a costimulatory function in T-cell activation [2].

We retrospectively analyzed the impact of standard-dose DPP-4 inhibitors (DPP-4i) on the development of acute and chronic GVHD (cGVHD) in diabetes mellitus patients undergoing allogeneic HCT between 2010 and 2019 at institutions participating in the Kanto Study Group for Cell Therapy (KSGCT). By using a clinical research form, information on the treatment for diabetes mellitus including DPP-4i until 100 days after HCT was collected. All patients provided informed consent for data reporting. This study was approved by the Institutional Review Board of Jichi Medical University Saitama Medical Center and each participating institution.

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

Data availability

The data of this study are not publicly available due to ethical restrictions in that it exceeds the scope of the recipient/donor’s consent for research use in the registry.

References

  1. Farag SS, Abu Zaid M, Schwartz JE, Thakrar TC, Blakley AJ, Abonour R, et al. Dipeptidyl Peptidase 4 Inhibition for Prophylaxis of Acute Graft-versus-Host Disease. N Engl J Med. 2021;384:11–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hatano R, Ohnuma K, Yamamoto J, Dang NH, Morimoto C. CD26-mediated co-stimulation in human CD8(+) T cells provokes effector function via pro-inflammatory cytokine production. Immunology. 2013;138:165–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Shulman HM, Sale GE, Lerner KG, Barker EA, Weiden PL, Sullivan K, et al. Chronic cutaneous graft-versus-host disease in man. Am J Pathol. 1978;91:545–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 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  PubMed  Google Scholar 

  5. Farag SS, Nelson R, Cairo MS, O’Leary HA, Zhang S, Huntley C, et al. High-dose sitagliptin for systemic inhibition of dipeptidylpeptidase-4 to enhance engraftment of single cord umbilical cord blood transplantation. Oncotarget. 2017;8:110350–7.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Farag SS, Srivastava S, Messina-Graham S, Schwartz J, Robertson MJ, Abonour R, et al. In vivo DPP-4 inhibition to enhance engraftment of single-unit cord blood transplants in adults with hematological malignancies. Stem Cells Dev. 2013;22:1007–15.

    Article  CAS  PubMed  Google Scholar 

  7. Herman GA, Stevens C, Van Dyck K, Bergman A, Yi B, De Smet M, et al. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharm Ther. 2005;78:675–88.

    Article  CAS  Google Scholar 

  8. Kim SC, Schneeweiss S, Glynn RJ, Doherty M, Goldfine AB, Solomon DH. Dipeptidyl peptidase-4 inhibitors in type 2 diabetes may reduce the risk of autoimmune diseases: a population-based cohort study. Ann Rheum Dis. 2015;74:1968–75.

    Article  CAS  PubMed  Google Scholar 

  9. Seong JM, Yee J, Gwak HS. Dipeptidyl peptidase-4 inhibitors lower the risk of autoimmune disease in patients with type 2 diabetes mellitus: A nationwide population-based cohort study. Br J Clin Pharm. 2019;85:1719–27.

    Article  CAS  Google Scholar 

  10. Chen YC, Chen TH, Sun CC, Chen JY, Chang SS, Yeung L, et al. Dipeptidyl peptidase-4 inhibitors and the risks of autoimmune diseases in type 2 diabetes mellitus patients in Taiwan: a nationwide population-based cohort study. Acta Diabetol. 2020;57:1181–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 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 Transpl. 2015;21:389–401.e381.

    Article  Google Scholar 

  12. Shulman HM, Cardona DM, Greenson JK, Hingorani S, Horn T, Huber E, et al. NIH Consensus development project on criteria for clinical trials in chronic graft-versus-host disease: II. The 2014 Pathology Working Group Report. Biol Blood Marrow Transpl. 2015;21:589–603.

    Article  Google Scholar 

Download references

Acknowledgements

The authors are grateful for the work of all of the physicians and data managers at the centers that contributed valuable data on transplantation to the KSGCT. We would also like to thank Toyohiro Kawano and all members of the KSGCT data center for their dedicated data management.

Author information

Authors and Affiliations

  1. Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan

    Shun-ichi Kimura, Kazuki Yoshimura, Hideki Nakasone & Yoshinobu Kanda

  2. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Hiroaki Shimizu & Noriko Doki

  3. Department of Hematology, Yokohama City University Medical Center, Kanagawa, Japan

    Takuya Miyazaki

  4. Department of Hematology, Kanagawa Cancer Center, Kanagawa, Japan

    Takuya Miyazaki, Takayoshi Tachibana & Masatsugu Tanaka

  5. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    Masatoshi Sakurai

  6. Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan

    Susumu Tanoue

  7. Department of Hematology, Chiba University Hospital, Chiba, Japan

    Kensuke Kayamori & Chikako Ohwada

  8. Department of Hematology, International University of Health and Welfare Narita Hospital, Chiba, Japan

    Chikako Ohwada

  9. Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Kanagawa, Japan

    Takuma Ohashi

  10. Department of Hematology, Aoba Municipal Hospital, Chiba, Japan

    Katsuhiro Shono

  11. Division of Hematology, Jichi Medical University, Tochigi, Japan

    Kaoru Hatano & Yoshinobu Kanda

  12. Department of Hematology, Tokyo Medical and Dental University, Tokyo, Japan

    Keigo Okada

  13. Department of Hematology, Saitama Medical Center, Saitama Medical University, Saitama, Japan

    Yuta Kimura

  14. Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan

    Sachiko Seo

  15. Department of Medicine, Division of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan

    Yoshihiro Hatta

  16. Division of Clinical Precision Research Platform, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan

    Satoshi Takahashi

Authors
  1. Shun-ichi Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroaki Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takuya Miyazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masatoshi Sakurai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Susumu Tanoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kensuke Kayamori
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chikako Ohwada
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kazuki Yoshimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hideki Nakasone
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Takuma Ohashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Katsuhiro Shono
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Takayoshi Tachibana
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kaoru Hatano
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Keigo Okada
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Yuta Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Sachiko Seo
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Noriko Doki
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Masatsugu Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Yoshihiro Hatta
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Satoshi Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Yoshinobu Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

the Kanto Study Group for Cell Therapy

Contributions

S-IK designed the study, analyzed data, and wrote the paper. HS, TM, MS, STanoue, KK, CO, KY, HN, TO, and KS advised on methods and revised the paper. TT, KH, KO, YKimura, SS, ND, MT, YH, and STakahashi collected data and revised the paper. YKanda designed the study, advised on the methods, wrote the paper, and was responsible for the project of the KSGCT.

Corresponding author

Correspondence to Yoshinobu Kanda.

Ethics declarations

Competing interests

S-IK has received personal fees from Asahi Kasei, Sumitomo Dainippon Pharma, Merck Sharp & Dohme, Astellas, Pfizer, Kyowa Kirin, Chugai Pharmaceutical Co., Ltd., Bristol-Myers Squibb, Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Amgen Co., Ltd., Meiji Seika Pharma Co., Ltd., and Nippon Kayaku. MS received research support from Nippon Shinyaku and owns stock in Celaid Therapeutics. HN has received honoraria from Takeda Pharmaceutical, Otsuka Pharmaceutical, Bristol-Myers Squibb, Pfizer, Novartis, Janssen Pharmaceutical, Eisai, Chugai Pharmaceutical, Sanofi, and Nippon Shinyaku. TT reports service on speakers bureaus from Otsuka, Novartis, Pfizer, MSD, abbvie, and Amgen, outside the submitted work. YKanda received honoraria from Merck Sharp & Dohme, Pfizer, Astellas Pharma, Janssen, Chugai Pharma, Otsuka, Sumitomo Dainippon Pharma, Eisai, Novartis, Kyowa Hakko Kirin, Bristol-Myers Squibb, Takeda Pharmaceuticals, Alexion Pharmaceuticals, Shire, Daiichi Sankyo, Ono Pharmaceutical, Nippon Shinyaku, Mochida Pharmaceutical, Mundipharma, Sanofi and Meiji Seika Kaisha, and research funding from Astellas Pharma, Eisai, Otsuka, Kyowa Hakko Kirin, Sanofi, Shionogi, Taiho Pharmaceutical, Chugai Pharma, Nippon Shinyaku and Pfizer. The other authors have no competing interests to declare.

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

Kimura, Si., Shimizu, H., Miyazaki, T. et al. Impact of standard-dose dipeptidyl peptidase-4 inhibitors on the incidence of graft-versus-host disease after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 58, 452–455 (2023). https://doi.org/10.1038/s41409-022-01901-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-022-01901-5

Search

Advanced search

Quick links