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.

  • Article
  • Published:

Posttransplantation cyclophosphamide vs. antithymocyte globulin as GVHD prophylaxis for mismatched unrelated hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 55, pages 349–355 (2020)Cite this article

Subjects

Abstract

Posttransplant cyclophosphamide (PT-Cy) is an efficient GVHD prophylaxis but has not been extensively evaluated in mismatched unrelated donor (MMUD) allo-HSCT, for which antithymocyte globulin (ATG) is still considered as a standard. Thus, we evaluated the outcome of MMUD allo-HSCT with PT-Cy (n = 22) and performed a historical comparison with a control group receiving ATG (n = 40) in a single center experience. Compared with the ATG group, the risk of grade 2–4 acute GVHD was significantly lower in the PT-Cy group (HR = 0.12, 95% CI = [0.03–0.48], p = 0.002). No difference was observed in the cumulative incidence of chronic GVHD. The risk of both NRM and relapse was significantly lower in the PT-Cy group (NRM: HR = 0.05, 95% CI = [0.00–0.63], p = 0.021; relapse: HR = 0.31; 95% CI = [0.09–1.10], p = 0.07). Thus, we observed significantly better PFS (HR = 0.22, 95% CI = (0.07–0.65); p = 0.006), OS (HR = 0.24, 95% CI = (0.07–0.84); p = 0.026), and GRFS (HR = 0.37, 95% CI = (0.17–0.80); p = 0.011) in the PT-Cy group. We conclude that PT-Cy is an effective GVHD prophylaxis in the setting of MMUD allo-HSCT, resulting in a better outcome compared with standard prophylaxis using ATG. This suggests that as it was shown in the setting of haploidentical allo-HSCT, the use of PT-Cy can overcome the impact of HLA disparity, leading to promising survivals that approach those observed after HLA matched allo-HSCT.

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
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Nowak J. Role of HLA in hematopoietic SCT. Bone Marrow Transpl. 2008;42 Suppl 2:S71–76.

    Article  CAS  Google Scholar 

  2. Eapen M, Klein JP, Sanz GF, Spellman S, Ruggeri A, Anasetti C, et al. Effect of donor–recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis. Lancet Oncol. 2011;12:1214–21.

    Article  CAS  Google Scholar 

  3. Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009;10:855–64.

    Article  CAS  Google Scholar 

  4. Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, et al. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. Lancet Oncol. 2016;17:164–73.

    Article  CAS  Google Scholar 

  5. Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transpl. 2008;14:641–50.

    Article  CAS  Google Scholar 

  6. Kanakry CG, O’Donnell PV, Furlong T, de Lima MJ, Wei W, Medeot M, et al. Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. J Clin Oncol. 2014;32:3497–505.

    Article  CAS  Google Scholar 

  7. Mielcarek M, Furlong T, ODonnell PV, Storer BE, McCune JS, Storb R, et al. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016;127:1502–8.

    Article  CAS  Google Scholar 

  8. Devillier R, Fürst S, Crocchiolo R, El-Cheikh J, Castagna L, Harbi S, et al. A conditioning platform based on fludarabine, busulfan, and 2 days of rabbit antithymocyte globulin results in promising results in patients undergoing allogeneic transplantation from both matched and mismatched unrelated donor. Am J Hematol. 2014;89:83–7.

    Article  CAS  Google Scholar 

  9. Fine J, Gray R. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.

    Article  Google Scholar 

  10. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transpl. 1995;15:825–8.

    CAS  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.e1.

    Article  Google Scholar 

  12. Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125:1333–8.

    Article  CAS  Google Scholar 

  13. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9.

    Article  CAS  Google Scholar 

  14. Armand P, Kim HT, Logan BR, Wang Z, Alyea EP, Kalaycio ME, et al. Validation and refinement of the disease risk index for allogeneic stem cell transplantation. Blood. 2014;123:3664–71.

    Article  CAS  Google Scholar 

  15. Ruggeri A, Labopin M, Bacigalupo A, Afanasyev B, Cornelissen JJ, Elmaagacli A, et al. Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT. J Hematol Oncol. 2018;11:40.

    Article  Google Scholar 

  16. Gaballa S, Ge I, El Fakih R, Brammer JE, Kongtim P, Tomuleasa C, et al. Results of a 2-arm, phase 2 clinical trial using post-transplantation cyclophosphamide for the prevention of graft-versus-host disease in haploidentical donor and mismatched unrelated donor hematopoietic stem cell transplantation. Cancer. 2016;122:3316–26.

    Article  CAS  Google Scholar 

  17. Kasamon YL, Ambinder RF, Fuchs EJ, Zahurak M, Rosner GL, Bolaños-Meade J, et al. Prospective study of nonmyeloablative, HLA-mismatched unrelated BMT with high-dose posttransplantation cyclophosphamide. Blood Adv. 2017;1:288–92.

    Article  CAS  Google Scholar 

  18. Jorge AS, Suárez-Lledó M, Pereira A, Gutierrez G, Fernández-Avilés F, Rosiñol L, et al. Single antigen–mismatched unrelated hematopoietic stem cell transplantation using high-dose post-transplantation cyclophosphamide is a suitable alternative for patients lacking HLA-matched donors. Biol Blood Marrow Transpl. 2018;24:1196–202.

    Article  CAS  Google Scholar 

  19. Mehta RS, Saliba RM, Chen J, Rondon G, Hammerstrom AE, Alousi A, et al. Post-transplantation cyclophosphamide versus conventional graft-versus-host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation. Br J Haematol. 2016;173:444–55.

    Article  CAS  Google Scholar 

  20. Wakamatsu M, Terakura S, Ohashi K, Fukuda T, Ozawa Y, Kanamori H, et al. Impacts of thymoglobulin in patients with acute leukemia in remission undergoing allogeneic HSCT from different donors. Blood Adv. 2019;3:105–15.

    Article  CAS  Google Scholar 

  21. Kumar A, Mhaskar AR, Reljic T, Mhaskar RS, Kharfan-Dabaja MA, Anasetti C, et al. Antithymocyte globulin for acute-graft-versus-host-disease prophylaxis in patients undergoing allogeneic hematopoietic cell transplantation: a systematic review. Leukemia. 2012;26:582–8.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the patients and the IPC transplantation staff.

Author information

Authors and Affiliations

  1. Department of Hematology, Institut Paoli-Calmettes, Marseille, France

    Charlotte Nykolyszyn, Angela Granata, Thomas Pagliardini, Samia Harbi, Reda Bouabdallah, Norbert Vey, Sabine Fürst, Valério Maisano, Faezeh Legrand, Pierre-Jean Weiller, Didier Blaise & Raynier Devillier

  2. Department of Hematology, Humanitas Cancer Center, Rozzano, Italy

    Luca Castagna

  3. Institut Paoli-Calmettes, Aix-Marseille Univ, CNRS, INSERM, CRCM, Marseille, France

    Norbert Vey, Christian Chabannon, Didier Blaise & Raynier Devillier

  4. Cell therapy facility, Institut Paoli-Calmettes, Marseille, France

    Claude Lemarié, Boris Calmels & Christian Chabannon

  5. CIC biothérapies: Inserm CBT-1409, Marseille, France

    Claude Lemarié, Boris Calmels & Christian Chabannon

Authors
  1. Charlotte Nykolyszyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Angela Granata
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Pagliardini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luca Castagna
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Samia Harbi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Reda Bouabdallah
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Norbert Vey
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sabine Fürst
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Valério Maisano
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Faezeh Legrand
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Claude Lemarié
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Boris Calmels
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Christian Chabannon
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Pierre-Jean Weiller
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Didier Blaise
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Raynier Devillier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Raynier Devillier.

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.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nykolyszyn, C., Granata, A., Pagliardini, T. et al. Posttransplantation cyclophosphamide vs. antithymocyte globulin as GVHD prophylaxis for mismatched unrelated hematopoietic stem cell transplantation. Bone Marrow Transplant 55, 349–355 (2020). https://doi.org/10.1038/s41409-019-0682-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-019-0682-2

This article is cited by

Search

Advanced search

Quick links