nature.com

Treatment of steroid resistant acute graft versus host disease with an anti-CD26 monoclonal antibody—Begelomab - Bone Marrow Transplantation

  • ️Locatelli, Franco
  • ️Fri Mar 13 2020

References

  1. Flowers ME, Inamoto Y, Carpenter PA, Lee SJ, Kiem HP, 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 

  2. 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.

    Article  Google Scholar 

  3. Ruutu T, Gratwohl A, de Witte T, Afanasyev B, Apperley J, Bacigalupo A, et al. Prophylaxis and treatment of GVHD: EBMT-ELN working group recommendations for a standardized practice. Bone Marrow Transpl. 2014;49:168–73.

    Article  CAS  Google Scholar 

  4. Mielcarek M, Storer BE, Boeckh M, Green ML, McDonald GB, Carpenter PA, et al. Initial therapy of acute graft-versus-host disease with low-dose prednisone does not compromise patient outcomes. Blood. 2009;113:2888–94.

    Article  CAS  Google Scholar 

  5. Van Lint MT, Milone G, Leotta S, Uderzo C, Scimè R, Dallorso S, et al. Treatment of acute graft-versus-host disease with prednisolone: significant survival advantage for day +5 responders and no advantage for nonresponders receiving anti-thymocyte globulin. Blood. 2006;107:4177–81.

    Article  Google Scholar 

  6. Lee SJ, Zahrieh D, Agura E, MacMillan M, Maziarz RT, McCarthy PL, et al. Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease:results of a randomized trial. Blood. 2004;104:1559–64.

    Article  CAS  Google Scholar 

  7. Macmillan ML, Couriel D, Weisdorf DJ, Schwab G, Havrilla G, Fleming N, et al. A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease. Blood. 2007;109:2657–62.

    Article  CAS  Google Scholar 

  8. Nature News. Stem-cell drug fails crucial trials. Nature. 2009. https://doi.org/10.1038/news.2009.894.

  9. Bolaños-Meade J, Logan BR, Alousi AM, Antin JH, Barowski K, Carter SL, et al. Phase 3 clinical trial of steroids/mycophenolate mofetil vs steroids/placebo as therapy for acute GVHD: BMT CTN 0802. Blood. 2014;124:3221–7.

    Article  Google Scholar 

  10. Xhaard A, Rocha V, Bueno B, Peffault de Latour R, Lenglet J, Petropoulou A, et al. SR acute GvHD: lack of improved long term survival usng new generation anticytokine therapy. Biol Blood Marrow Transpl. 2012;18:406–13.

    Article  CAS  Google Scholar 

  11. Ohnuma K, Dang NH, Morimoto C. Revisiting an old acquaintance: CD26 and its molecular mechanisms in T cell function. Trends Immunol. 2008;29:295–300.

    Article  CAS  Google Scholar 

  12. Hatano R, Ohnuma K, Yamamoto J, Dang NH, Yamada T, Morimoto C. Humanized monoclonal antibody specific for CD26 ameliorates xenogeneic GVHD by human lymphocytes. Br J Haematol. 2013;162:263.

    Article  CAS  Google Scholar 

  13. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift R, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304.

    Article  CAS  Google Scholar 

  14. Axt L, Naumann A, Toennies JH, Haen SP, Vogel W, Schneidawind D, et al. Retrospective single center analysis of outcome, risk factors and therapy in SR graft-versus-host disease after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2019. https://doi.org/10.1038/s41409-019-0544-y.

  15. Jagasia M, Greinix H, Robin M, Das Gupta E, Jacobs R, Savani BP, et al. Extracorporeal photopheresis versus anticytokine therapy as a second-line treatment for steroid-refractory acute GVHD: a multicenter comparative analysis. Biol Blood Marrow Transplant. 2013;19:1129–33.

    Article  CAS  Google Scholar 

  16. Ringden O, Arjang Baygan A, Remberger M, Gustafsson B, Winiarski CJ, Khoein B, et al. Placenta-derived decidua stromal cells for treatment of severe acute graft-versus-host disease. Stem Cells Transl Med. 2018;7:325–32.

    Article  CAS  Google Scholar 

  17. Groth C, Lenneke G, van Groningen FJ, Matos TR, Bremmers ME, Preijers FWMB, et al. Phase I/II trial of a combination of anti-CD3/CD7 immunotoxins for steroid-refractory acute graft-versus-host disease. Biol Blood Marrow Transpl. 2019;25:712719.

    Article  Google Scholar 

  18. Fløisand Y, Lazarevic VLJ, Maertens J, Mattsson J, Shah VN, Zachee P, et al. Safety and effectiveness of vedolizumab in patients with steroid- refractory gastrointestinal acute graft-versus-host disease: a retrospective record review. Biol Blood Marrow Transpl. 2019;25:720–7.

    Article  Google Scholar 

  19. Marcondes AM, Hockenbery D, Lesnikova M, Dinarello CA, Woolfrey A, Gernsheimer T, et al. Response of steroid-refractory acute GVHD to a1-antitrypsin. Biol Blood Marrow Transpl. 2016;22:1596–601.

    Article  CAS  Google Scholar 

  20. Bader P, Kuçi Z, Bakhtiar S, Basu O, Bug G, Dennis M, et al. Effective treatment of steroid and therapy-refractory acute graft-versus-host disease with a novel mesenchymal stromal cell product (MSC-FFM). Bone Marrow Transplant. 2018;53:852–62.

    Article  CAS  Google Scholar 

  21. Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015;29:2062–8.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by FARITMO, Genova Italy and Associazione Italian Ricerca contro il Cancro (AIRC), Milano, Italy. We thank ADIENNE SA Lugano Switzerland, for the generous supply of Begelomab in the compassionate use study. We thank the nurses of our transplant centers for excellent care of these difficult patients.

Author information

Authors and Affiliations

  1. Universita’ Cattolica del Sacro Cuore, Roma, Italy

    Andrea Bacigalupo, Patrizia Chiusolo & Simona Sica

  2. Istituto di Ematologia, Fondazione Policlinico Universitario Gemelli, IRCCS, Roma, Italy

    Andrea Bacigalupo

  3. UOC Ematologia e Trapianto di Midollo Osseo, IRCCS Ospedale Policlinico San Martino Genova, Genova, Italy

    Emanuele Angelucci, Anna Maria Raiola, Riccardo Varaldo, Carmen Di Grazia & Francesca Gualandi

  4. Department of Translational Research on New Technology in Medicine and Surgery; Universita’ di Pisa, Pisa, Italy

    Edoardo Benedetti

  5. Dipartimento di Medicina Clinica e Chirurgica, Universita’ Federico II, Napoli, Italy

    Antonio Risitano

  6. UOC di oncoematologia e TMO, Dipartimento Oncologico “la Maddalena”, Palermo, Italy

    Maurizio Musso

  7. Divisione di Ematologia, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy

    Francesco Zallio

  8. IRCCS Ospedale San Raffaele; University Vita-Salute San Raffaele, Milano, Italy

    Fabio Ciceri

  9. Universita’ Cattolica del Sacro Cuore, Roma, Italy

    Patrizia Chiusolo & Simona Sica

  10. Dipartimento di Oncologia ed Ematologia Università di Milano e Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Bergamo, Italy

    Alessandro Rambaldi

  11. Department of Hematology “L. & A. Seràgnoli” University Hospital S. Orsola-Malpighi, Bologna, Italy

    Francesca Bonifazi

  12. Istituto di Ematologia, Ospedale S Gerardo, Monza, Italy

    Matteo Parma

  13. Centro Trapianti Midollo Osseo, Grande Ospedale Metropolitano “BMM”, Reggio Calabria, Calabria, Italy

    Massimo Martino

  14. Hematology-BMT Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico – University of Milan, Milano, Italy

    Francesco Onida

  15. UOC Ematologia, Policlinico Umberto 1, Roma, Italy

    Anna Paola Iori

  16. Divisione di Ematologia, Ospedale S Giovanni di Dio, Salerno, Italy

    Carmine Selleri

  17. Divisione di Ematologia, Ospedale San Bortolo, Vicenza, Italy

    Carlo Borghero

  18. Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, USA

    Alice Bertaina

  19. UO Ematologia e CTMO, Universita’ di Parma, Parma, Italy

    Lucia Prezioso

  20. Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu’, Sapienza, Università di Roma, Roma, Italy

    Mattia Algeri & Franco Locatelli

Authors

  1. Andrea Bacigalupo

    You can also search for this author inPubMed Google Scholar

  2. Emanuele Angelucci

    You can also search for this author inPubMed Google Scholar

  3. Anna Maria Raiola

    You can also search for this author inPubMed Google Scholar

  4. Riccardo Varaldo

    You can also search for this author inPubMed Google Scholar

  5. Carmen Di Grazia

    You can also search for this author inPubMed Google Scholar

  6. Francesca Gualandi

    You can also search for this author inPubMed Google Scholar

  7. Edoardo Benedetti

    You can also search for this author inPubMed Google Scholar

  8. Antonio Risitano

    You can also search for this author inPubMed Google Scholar

  9. Maurizio Musso

    You can also search for this author inPubMed Google Scholar

  10. Francesco Zallio

    You can also search for this author inPubMed Google Scholar

  11. Fabio Ciceri

    You can also search for this author inPubMed Google Scholar

  12. Patrizia Chiusolo

    You can also search for this author inPubMed Google Scholar

  13. Simona Sica

    You can also search for this author inPubMed Google Scholar

  14. Alessandro Rambaldi

    You can also search for this author inPubMed Google Scholar

  15. Francesca Bonifazi

    You can also search for this author inPubMed Google Scholar

  16. Matteo Parma

    You can also search for this author inPubMed Google Scholar

  17. Massimo Martino

    You can also search for this author inPubMed Google Scholar

  18. Francesco Onida

    You can also search for this author inPubMed Google Scholar

  19. Anna Paola Iori

    You can also search for this author inPubMed Google Scholar

  20. Carmine Selleri

    You can also search for this author inPubMed Google Scholar

  21. Carlo Borghero

    You can also search for this author inPubMed Google Scholar

  22. Alice Bertaina

    You can also search for this author inPubMed Google Scholar

  23. Lucia Prezioso

    You can also search for this author inPubMed Google Scholar

  24. Mattia Algeri

    You can also search for this author inPubMed Google Scholar

  25. Franco Locatelli

    You can also search for this author inPubMed Google Scholar

Contributions

AB, FL, and FC designed the studies, contributed patients, analyzed the data and wrote the manuscript; FG, AMR, RV, CDG, EA, ARi, ARa, MM, FZ, PC, SS, AR, FB, MP, FO, API, CS, CB, AB, MA contributed patients and revised the paper.

Corresponding author

Correspondence to Andrea Bacigalupo.

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.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bacigalupo, A., Angelucci, E., Raiola, A.M. et al. Treatment of steroid resistant acute graft versus host disease with an anti-CD26 monoclonal antibody—Begelomab. Bone Marrow Transplant 55, 1580–1587 (2020). https://doi.org/10.1038/s41409-020-0855-z

Download citation

  • Received: 30 September 2019

  • Revised: 20 February 2020

  • Accepted: 28 February 2020

  • Published: 13 March 2020

  • Issue Date: August 2020

  • DOI: https://doi.org/10.1038/s41409-020-0855-z