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:

Addition and drug monitoring of mycophenolate mofetil for GVHD prophylaxis in unrelated bone marrow transplantation

Bone Marrow Transplantation volume 57, pages 1198–1200 (2022)Cite this article

Subjects

Human leukocyte antigen 1-locus-mismatched unrelated donor (1MMUD) transplantation impairs survival owing to the increased risk of graft-versus-host-disease (GVHD) and graft failure, thereby indicating that the standard combination of a calcineurin inhibitor (CNI) plus methotrexate (MTX) affords limited efficacy for GVHD prophylaxis in 1MMUD transplantation [1,2,3]. To overcome this, we combined mycophenolate mofetil (MMF), a mycophenolic acid (MPA) prodrug that suppresses the proliferation of activated lymphocytes by inhibiting de novo purine biosynthesis, with CNI and MTX for GVHD prophylaxis in 1MMUD transplantation [4].

Several studies, including a previous study from our institution, have demonstrated the utility of the triple combination of CNI, MTX, and MMF for GVHD prophylaxis in transplants from HLA-matched unrelated donors [5, 6]. However, studies assessing the triple combination in 1MMUD transplantation remain scarce. Therefore, we performed a retrospective cohort study to compare outcomes of patients who received a 1MMUD transplant with conventional GVHD prophylaxis using CNI and MTX (1MM-double) and GVHD prophylaxis with the triple combination (1MM-triple). Given that our institute has previously demonstrated the importance of therapeutic monitoring of MMF for effective GVHD prophylaxis in cord blood transplantation (CBT), we evaluated the effect of plasma levels of MPA, an active form of MMF, on transplant outcomes in 1MM-triple transplantation [7, 8].

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The impact of GVHD prophylaxis regimen and MPA levels in 1MM-triple transplant.

Data availability

The datasets generation during and/or analysed during the current study can be accessed from the corresponding author on reasonable request.

References

  1. Morishima Y, Sasazuki T, Inoko H, Juji T, Akaza T, Yamamoto K, et al. The clinical significance of human leukocyte antigen (HLA) allele compatibility in patients receiving a marrow transplant from serologically HLA-A, HLA-B, and HLA-DR matched unrelated donors. Blood. 2002;99:4200–6.

    Article  CAS  Google Scholar 

  2. Flomenberg N, Baxter-Lowe LA, Confer D, Fernandez-Vina M, Filipovich A, Horowitz M, et al. Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome. Blood. 2004;104:1923–30.

    Article  CAS  Google Scholar 

  3. Kanda J, Ichinohe T, Fuji S, Maeda Y, Ohashi K, Fukuda T, et al. Impact of HLA mismatch direction on the outcome of unrelated bone marrow transplantation: a retrospective analysis from the Japan Society for Hematopoietic Cell Transplantation. Biol Blood Marrow Transpl. 2015;21:305–11.

    Article  Google Scholar 

  4. Eugui EM, Allison AC. Immunosuppressive activity of mycophenolate mofetil. Ann N. Y Acad Sci. 1993;685:309–29.

    Article  CAS  Google Scholar 

  5. Lai Y, Ma J, Schwarzenberger P, Li W, Cai Z, Zhou J, et al. Combination of CsA, MTX and low-dose, short-course mycophenolate mofetil for GVHD prophylaxis. Bone Marrow Transpl. 2009;43:61–67.

    Article  CAS  Google Scholar 

  6. Mizumoto C, Kanda J, Ichinohe T, Ishikawa T, Matsui M, Kadowaki N, et al. Mycophenolate mofetil combined with tacrolimus and minidose methotrexate after unrelated donor bone marrow transplantation with reduced-intensity conditioning. Int J Hematol. 2009;89:538–45.

    Article  CAS  Google Scholar 

  7. Arai Y, Kondo T, Kitano T, Hishizawa M, Yamashita K, Kadowaki N, et al. Monitoring mycophenolate mofetil is necessary for the effective prophylaxis of acute GVHD after cord blood transplantation. Bone Marrow Transpl. 2015;50:312–4.

    Article  CAS  Google Scholar 

  8. Muranushi H, Kanda J, Arai Y, Shindo T, Hishizawa M, Yamamoto T, et al. Drug monitoring for mycophenolic acid in graft-versus-host disease prophylaxis in cord blood transplantation. Br J Clin Pharmacol. 2020;86:2464–72.

  9. Okamura A, Yamamori M, Shimoyama M, Kawano Y, Kawano H, Kawamori Y, et al. Pharmacokinetics-based optimal dose-exploration of mycophenolate mofetil in allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2008;88:104–10.

    Article  CAS  Google Scholar 

  10. Giaccone L, McCune JS, Maris MB, Gooley TA, Sandmaier BM, Slattery JT, et al. Pharmacodynamics of mycophenolate mofetil after nonmyeloablative conditioning and unrelated donor hematopoietic cell transplantation. Blood. 2005;106:4381–8.

    Article  CAS  Google Scholar 

  11. Haentzschel I, Freiberg-Richter J, Platzbecker U, Kiani A, Schetelig J, Illmer T, et al. Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation. Bone Marrow Transpl. 2008;42:113–20.

    Article  CAS  Google Scholar 

  12. McDermott CL, Sandmaier BM, Storer B, Li H, Mager DE, Boeckh MJ, et al. Nonrelapse mortality and mycophenolic acid exposure in nonmyeloablative hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2013;19:1159–66.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Emi Furusaka, Tomoko Okuda, Miki Shirasu, and Megumi Oka for their expert data management and secretarial assistance and the transplantation team members at Kyoto University Hospital for their dedicated care of patients and donors.

Funding

This study was supported by Management Expenses Grants of Kyoto University from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (to T. Kondo).

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Fumiya Wada, Tadakazu Kondo, Yasuyuki Arai, Chisato Mizumoto, Junya Kanda, Toshio Kitawaki, Kouhei Yamashita & Akifumi Takaori-Kondo

  2. Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan

    Ryusuke Yamamoto

  3. Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan

    Takero Yamagiwa

Authors
  1. Fumiya Wada
    View author publications

    Search author on:PubMed Google Scholar

  2. Tadakazu Kondo
    View author publications

    Search author on:PubMed Google Scholar

  3. Ryusuke Yamamoto
    View author publications

    Search author on:PubMed Google Scholar

  4. Takero Yamagiwa
    View author publications

    Search author on:PubMed Google Scholar

  5. Yasuyuki Arai
    View author publications

    Search author on:PubMed Google Scholar

  6. Chisato Mizumoto
    View author publications

    Search author on:PubMed Google Scholar

  7. Junya Kanda
    View author publications

    Search author on:PubMed Google Scholar

  8. Toshio Kitawaki
    View author publications

    Search author on:PubMed Google Scholar

  9. Kouhei Yamashita
    View author publications

    Search author on:PubMed Google Scholar

  10. Akifumi Takaori-Kondo
    View author publications

    Search author on:PubMed Google Scholar

Contributions

FW, RY, and TK designed this study. TK organized the project. FW and RY performed the statistical analyses. YA, CM, JK, TK, KY, and AT-K interpreted data. FW wrote the first draft of the manuscript. All other authors critically reviewed the draft and approved the final version of the manuscript.

Corresponding author

Correspondence to Tadakazu Kondo.

Ethics declarations

Competing interests

The authors declare no competing interests.

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

Wada, F., Kondo, T., Yamamoto, R. et al. Addition and drug monitoring of mycophenolate mofetil for GVHD prophylaxis in unrelated bone marrow transplantation. Bone Marrow Transplant 57, 1198–1200 (2022). https://doi.org/10.1038/s41409-022-01692-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41409-022-01692-9

This article is cited by

Search

Advanced search

Quick links