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:

Severity of mucositis during allogeneic transplantation impacts post-transplant cyclosporin absorption

Bone Marrow Transplantation volume 55, pages 1857–1859 (2020)Cite this article

Subjects

Cyclosporin A (CsA) is frequently used as graft-versus-host disease (GVHD) prophylaxis following allogeneic haematopoietic stem cell transplantation (allo-HSCT). Inadequate concentrations of CsA are associated with increased GVHD risk [1]. High concentrations of CsA have been associated with increased disease relapse risk, cyclosporin toxicity including acute kidney injury and increased transplant related mortality [2, 3]. Given the importance of CsA levels for post-transplant outcomes, an understanding of the factors that impact CsA absorption is critical to guiding post-transplant CsA dosing. Gastrointestinal mucositis may impact on oral drug absorption across the injured epithelial barrier as well as via altered drug transport and efflux systems. The impact of gastrointestinal mucositis on subsequent oral CsA absorption post transplant is unclear.

This study determined the relationship between the degree of mucositis during transplant, serum CsA concentrations, and subsequent transplant outcomes. We assessed patients who underwent allogeneic stem cell transplantation between 2002 and 2015 at the Royal Melbourne Hospital. We determined the relationship between mucositis severity and peak serum orally-administered C2 CsA concentration (peak serum concentration taken 2 h post dose) up to D + 100 post-transplant. We further determined the relationships between mean C2 CsA concentrations and acute GVHD (aGVHD) incidence, severity of renal impairment, cytomegalovirus (CMV) reactivation, and disease relapse.

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

Fig. 1

References

  1. Rogosheske JR, Fargen AD, DeFor TE, Warlick E, Arora M, Blazar BR, et al. Higher therapeutic CsA levels early post transplantation reduce risk of acute GVHD and improves survival. Bone Marrow Transpl. 2014;49:122–5.

    Article  CAS  Google Scholar 

  2. Inamoto Y, Flowers MED, Lee SJ, Carpenter PA, Warren EH, Deeg HJ, et al. Influence of immunosuppressive treatment on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation. Blood. 2011;118(Jul):456–63.

    Article  CAS  Google Scholar 

  3. da Silva JB, de Melo Lima MH, Secoli SR. Influence of cyclosporine on the occurrence of nephrotoxicity after allogeneic hematopoietic stem cell transplantation: a systematic review. Rev Bras Hematol Hemoter. 2014;36:363–8.

    Article  Google Scholar 

  4. Harris AC, Young R, Devine S, Hogan WJ, Ayuk F, Bunworasate U, et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the mount sinai acute GVHD International Consortium. Biol Blood Marrow Transpl. 2016;22:4–10.

    Article  Google Scholar 

  5. Vokurka S, Steinerova K, Karas M, Koza V. Characteristics and risk factors of oral mucositis after allogeneic stem cell transplantation with FLU/MEL conditioning regimen in context with BU/CY2. Bone Marrow Transpl. 2009;44:601–5.

    Article  CAS  Google Scholar 

  6. Malard F, Szydlo RM, Brissot E, Chevallier P, Guillaume T, Delaunay J, et al. Impact of cyclosporine-A concentration on the incidence of severe acute graft-versus-host disease after allogeneic stem cell transplantation. Biol Blood Marrow Transpl. 2010;16:28–34.

    Article  CAS  Google Scholar 

  7. Locatelli F, Zecca M, Rondelli R, Bonetti F, Dini G, Prete A, et al. Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA-identical sibling bone marrow transplantation: results of a randomized trial. Blood. 2000;95:1572–9.

    Article  CAS  Google Scholar 

  8. Kato M, Kurata M, Kanda J, Kato K, Tomizawa D, Kudo K, et al. Impact of graft-versus-host disease on relapse and survival after allogeneic stem cell transplantation for pediatric leukemia. Bone Marrow Transpl. 2019;54:68–75.

    Article  Google Scholar 

  9. Correa ME, Schubert MM, Storer B, Martin PJ, Flowers MED. Correlation between severity of oral mucositis and both overall and gut acute GvHD after high intensity conditioning hematopoietic stem cell transplantation. Blood. 2012;120–1.

Download references

Author information

Authors and Affiliations

  1. Bone Marrow Transplant Service, Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia

    Joanne L. C. Tan, Eric Wong, Ashish Bajel, Radha Ramanan, Andrew B. M. Lim & David S. Ritchie

  2. Department of Clinical Haematology and Bone Marrow Transplantation, The Alfred Hospital, Prahan, VIC, Australia

    Joanne L. C. Tan

  3. Department of Clinical Haematology and Bone Marrow Transplant Service, The Austin Hospital, Heidelberg, VIC, Australia

    Eric Wong & Andrew B. M. Lim

Authors
  1. Joanne L. C. Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ashish Bajel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Radha Ramanan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrew B. M. Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David S. Ritchie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joanne L. C. Tan.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tan, J.L.C., Wong, E., Bajel, A. et al. Severity of mucositis during allogeneic transplantation impacts post-transplant cyclosporin absorption. Bone Marrow Transplant 55, 1857–1859 (2020). https://doi.org/10.1038/s41409-020-0795-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-020-0795-7

Search

Advanced search

Quick links