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:

Necessity for treatment of steroid refractory severe GIT GVHD: patience of providers

Bone Marrow Transplantation volume 55, pages 833–835 (2020)Cite this article

Subjects

To the Editor,

Steroid-refractory gastrointestinal tract (GIT) acute graft-versus-host disease (SR-aGVHD) remains one the most lethal complications of allogeneic hematopoietic cell transplantation (HCT), with a mortality rate upwards of 75% [1, 2]. Despite the utility of various therapies, complete remission rates can average only at 30% [3]. Affected patients are treated with alternative and higher intensity immunosuppressive drugs to prevent tissue injury caused by immune attack mostly by alloreactive T cells. However, these patients have also deficiency in tissue regeneration and repair. It has been shown that severe GVHD is characterized by an imbalance of circulating tissue repair factors, with elevated amphiregulin and very low (<10 pg/ml) plasma epidermal growth factor (EGF). In addition to this, a urinary-derived preparation of human chorionic gonadotropin (hCG) improved chronic GVHD involving the skin and GIT [4]. The authors found that the expression of indoleamine-2,3-dioxygenase, and regulatory T cells (Tregs) were expanded [4]. Holtan et al. recently used human chorionic gonadotropin [Pregnyl® (EGF and hCG)], in a phase I study for treatment of steroid refractory acute GVHD [5]. At day 28 of study, responses for initial therapy were 8/13 CR (62%), 0/13 PR (0%), and 5/13 NR (38%). Increased serum hCG, estradiol, and testosterone plasma EGF Treg expansion were observed in patients compared with baseline. GIT GVHD is one of the protein-losing enteropathies associated with mucosal erosions [6, 7]. Albumin levels are consistently very low in these patients and hence also useful in predicting the occurrence of severe aGVHD [8], as well as its outcome (e.g., mortality) [9]. We present a case that demonstrates that the recovery of GIT of injury, tissue healing, and regeneration from GIT GVHD is a very slow and difficult process and takes long-time.

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. Castilla-Llorente C, Martin PJ, McDonald GB, Storer BE, Appelbaum FR, Deeg HJ, et al. Prognostic factors and outcomes of severe gastrointestinal GVHD after allogeneic hematopoietic cell transplantation. Bone Marrow Transpl. 2014;49:966–71. https://doi.org/10.1038/bmt.2014.69

    Article  CAS  Google Scholar 

  2. Ustun C, Jillella A, Shah R, Sterling K, Deremer D, Savage N, et al. Second allo-SCT from a different donor can improve severe steroid-resistant gut GVHD. Bone Marrow Transpl. 2010;45:1658–60. https://doi.org/10.1038/bmt.2010.17

    Article  CAS  Google Scholar 

  3. Martin PJ, Rizzo JD, Wingard JR, Ballen K, Curtin PT, Cutler C, et al. First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transpl. 2012;18:1150–63. https://doi.org/10.1016/j.bbmt.2012.04.005

    Article  Google Scholar 

  4. Elmaagacli AH, Ditschkowski M, Steckel NK, Gromke T, Ottinger H, Hillen U, et al. Human chorionic gonadotropin and indolamine 2,3-dioxygenase in patients with GVHD. Bone Marrow Transpl. 2014;49:800–5. https://doi.org/10.1038/bmt.2014.59

    Article  CAS  Google Scholar 

  5. Holtan S, Hoeschen A, Cao Q, Arora M, Bachanova V, Brunstein C, et al. Facilitating resolution of life-threatening acute graft-versus-host disease by supplementation of human chorionic gonadotropin and epidermal growth factor (Pregnyl): a phase I study. Blood. 2018;132:71.

  6. Weisdorf SA, Salati LM, Longsdorf JA, Ramsay NK, Sharp HL. Graft-versus-host disease of the intestine: a protein losing enteropathy characterized by fecal alpha 1-antitrypsin. Gastroenterology. 1983;85:1076–81.

    Article  CAS  Google Scholar 

  7. Levitt DG, Levitt MD. Protein losing enteropathy: comprehensive review of the mechanistic association with clinical and subclinical disease states. Clin Exp Gastroenterol. 2017;10:147–68. https://doi.org/10.2147/CEG.S136803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Rashidi A, DiPersio JF, Westervelt P, Abboud CN, Schroeder MA, Cashen AF, et al. Peritransplant serum albumin decline predicts subsequent severe acute graft-versus-host disease after mucotoxic myeloablative conditioning. Biol Blood Marrow Transpl. 2016;22:1137–41. https://doi.org/10.1016/j.bbmt.2016.03.010

    Article  Google Scholar 

  9. Rezvani AR, Storer BE, Storb RF, Mielcarek M, Maloney DG, Sandmaier BM, et al. Decreased serum albumin as a biomarker for severe acute graft-versus-host disease after reduced-intensity allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2011;17:1594–601. https://doi.org/10.1016/j.bbmt.2011.07.021

    Article  CAS  Google Scholar 

  10. Horvathy DB, Simon M, Schwarz CM, Masteling M, Vacz G, Hornyak I, et al. Serum albumin as a local therapeutic agent in cell therapy and tissue engineering. Biofactors. 2017;43:315–30. https://doi.org/10.1002/biof.1337

    Article  CAS  PubMed  Google Scholar 

  11. Dave M, Loftus EV Jr. Mucosal healing in inflammatory bowel disease-a true paradigm of success? Gastroenterol Hepatol. 2012;8:29–38. e-pub ahead of print 2012/02/22

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology, Oncology and Cellular Therapy, Rush University, Chicago, IL, USA

    Celalettin Ustun, Jacqueline Baptista, Debra A. Marinovic, Marisa Mozer, Mallory Weber & Sunita Nathan

  2. Rosalind Franklin University of Medicine and Science, College of Pharmacy, 3333 Green Bay Road, North Chicago, IL, 30064, USA

    Eris Tollkuci

  3. Rush University Medical Center, Division of Pharmacy, 1653 West Congress Parkway, Chicago, IL, 60612, USA

    Eris Tollkuci

  4. Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA

    Armin Rashidi, Shernan Holtan & Daniel Weisdorf

  5. Division of Digestive Diseases and Nutrition, Rush University, Chicago, IL, USA

    Ece Mutlu

Authors
  1. Celalettin Ustun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jacqueline Baptista
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Debra A. Marinovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eris Tollkuci
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marisa Mozer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Armin Rashidi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mallory Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ece Mutlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shernan Holtan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Daniel Weisdorf
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sunita Nathan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Celalettin Ustun.

Ethics declarations

Conflict of interest

The authors declare that they have 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

Ustun, C., Baptista, J., Marinovic, D.A. et al. Necessity for treatment of steroid refractory severe GIT GVHD: patience of providers. Bone Marrow Transplant 55, 833–835 (2020). https://doi.org/10.1038/s41409-019-0630-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-019-0630-1

Search

Advanced search

Quick links