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:

Evaluation of infectious complications after haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide following reduced-intensity and myeloablative conditioning: a study on behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC)

Bone Marrow Transplantation volume 54, pages 1586–1594 (2019)Cite this article

Subjects

Abstract

Several approaches have been developed to overcome historical barriers associated with poor outcomes in the setting of HLA-haploidentical allogeneic transplantation (HaploSCT). Here, we examine the outcome of patients with various hematological disorders undergoing HaploSCT with high-dose, post-transplantation cyclophosphamide. We performed a retrospective study on 381 patients from 30 centers between January 2013 and December 2015. At the last follow-up, a total of 1058 infectious episodes were diagnosed, affecting 90.3% of the cohort. Median time to first infection was 13 days for bacterial, 32 days for viral and 20 days for fungal infections. Around 41% of these infections were of bacterial origin and 35% of viral origin, among which 48.8% of patients presented CMV reactivation. Median of GVHD relapse-free survival, progression-free survival and overall survival were 7.1 months, 19.9 months and 33.5 months, respectively. HSCT procedure was the primary or contributing cause of death (55.6%), followed by relapse of the original disease (34.2%). Infections accounted for 45.7% of the HSCT-related deaths. The present multicenter data on a large cohort of patients receiving HaploSCT with PTCy confirmed the feasibility of the procedure with an acceptable incidence of infectious complications, not different as compared to other haploidentical platforms or HLA-matched transplantation.

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

Similar content being viewed by others

References

  1. Beatty PG, Clift RA, Mickelson EM, Nisperos BB, Flournoy N, Martin PJ, et al. Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med. 1985;313:765–71.

    Article  CAS  PubMed  Google Scholar 

  2. Ciurea SO, Mulanovich V, Saliba RM, Bayraktar UD, Jiang Y, Bassett R, et al. Improved early outcomes using a T cell replete graft compared with T cell depleted haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2012;18:1835–44.

    Article  PubMed  PubMed Central  Google Scholar 

  3. O’Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8:377–86.

    Article  PubMed  Google Scholar 

  4. 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 Transplant. 2008;14:641–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cho B-S, Yoon J-H, Shin S-H, Yahng S-A, Lee S-E, Eom K-S, et al. Comparison of allogeneic stem cell transplantation from familial-mismatched/haploidentical donors and from unrelated donors in adults with high-risk acute myelogenous leukemia. Biol Blood Marrow Transplant. 2012;18:1552–63.

    Article  PubMed  Google Scholar 

  6. Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, et al. Haploidentical transplantation using T cell replete peripheral blood stem cells and myeloablative conditioning in patients with high-risk hematologic malignancies who lack conventional donors is well tolerated and produces excellent relapse-free survival: results of a prospective phase II trial. Biol Blood Marrow Transplant. 2012;18:1859–66.

    Article  PubMed  Google Scholar 

  7. Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, et al. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transplant. 2013;19:117–22.

    Article  CAS  PubMed  Google Scholar 

  8. Sahin U, Toprak SK, Atilla PA, Atilla E, Demirer T. An overview of infectious complications after allogeneic hematopoietic stem cell transplantation. J Infect Chemother. 2016;22:505–14.

    Article  PubMed  Google Scholar 

  9. Crocchiolo R, Bramanti S, Vai A, Sarina B, Mineri R, Casari E, et al. Infections after T-replete haploidentical transplantation and high-dose cyclophosphamide as graft-versus-host disease prophylaxis. Transpl Infect Dis. 2015;17:242–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Slade M, Goldsmith S, Romee R, DiPersio JF, Dubberke ER, Westervelt P et al. Epidemiology of infections following haploidentical peripheral blood hematopoietic cell transplantation. Transpl Infect Dis. 2017;19:1–10.

  11. Castagna L, Crocchiolo R, Furst S, Bramanti S, El Cheikh J, Sarina B, et al. Bone marrow compared with peripheral blood stem cells for haploidentical transplantation with a nonmyeloablative conditioning regimen and post-transplantation cyclophosphamide. Biol Blood Marrow Transplant. 2014;20:724–9.

    Article  PubMed  Google Scholar 

  12. Brissot E, Alsuliman T, Gruson B, Hermet E, Tirefort Y, Yakoub-Agha I, et al. [How to manage EBV reactivation and EBV-PTLD, CMV and human herpesvirus 6 reactivation and infection after allogeneic stem cell transplantation: A report of the SFGM-TC (update)]. Bull Cancer. 2017;104:S181–S187.

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  14. Arora M, Klein JP, Weisdorf DJ, Hassebroek A, Flowers MED, Cutler CS, et al. Chronic GVHD risk score: a Center for International Blood and Marrow Transplant Research analysis. Blood. 2011;117:6714–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Aversa F, Prezioso L, Manfra I, Galaverna F, Spolzino A, Monti A. Immunity to Infections after Haploidentical Hematopoietic Stem Cell Transplantation. Mediterr J Hematol Infect Dis. 2016;8:e2016057.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Fabricius WA, Ramanathan M. Review on haploidentical hematopoietic cell transplantation in patients with hematologic malignancies. Adv Hematol. 2016;2016:5726132.

    PubMed  PubMed Central  Google Scholar 

  17. Atilla E, Atilla PA, Bozdağ SC, Demirer T. A review of infectious complications after haploidentical hematopoietic stem cell transplantations. Infection. 2017;45:403–11.

    Article  CAS  PubMed  Google Scholar 

  18. Young J-AH, Logan BR, Wu J, Wingard JR, Weisdorf DJ, Mudrick C, et al. Infections after transplantation of bone marrow or peripheral blood stem cells from unrelated donors. Biol Blood Marrow Transplant. 2016;22:359–70.

    Article  PubMed  Google Scholar 

  19. Mikulska M, Del Bono V, Bruzzi P, Raiola AM, Gualandi F, Van Lint MT, et al. Mortality after bloodstream infections in allogeneic haematopoietic stem cell transplant (HSCT) recipients. Infection. 2012;40:271–8.

    Article  CAS  PubMed  Google Scholar 

  20. Wingard JR, Hsu J, Hiemenz JW. Hematopoietic stem cell transplantation: an overview of infection risks and epidemiology. Infect Dis Clin North Am. 2010;24:257–72.

    Article  PubMed  Google Scholar 

  21. Mikulska M, Del Bono V, Viscoli C. Bacterial infections in hematopoietic stem cell transplantation recipients. Curr Opin Hematol. 2014;21:451–8.

    Article  CAS  PubMed  Google Scholar 

  22. Valadkhani B, Kargar M, Ashouri A, Hadjibabaie M, Gholami K, Ghavamzadeh A. The risk factors for cytomegalovirus reactivation following stem cell transplantation. J Res Pharm Pract. 2016;5:63–9.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Arthur RR, Shah KV, Charache P, Saral R. BK and JC virus infections in recipients of bone marrow transplants. J Infect Dis. 1988;158:563–9.

    Article  CAS  PubMed  Google Scholar 

  24. Lunde LE, Dasaraju S, Cao Q, Cohn CS, Reding M, Bejanyan N, et al. Hemorrhagic cystitis after allogeneic hematopoietic cell transplantation: risk factors, graft source and survival. Bone Marrow Transplant. 2015;50:1432–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gilis L, Morisset S, Billaud G, Ducastelle-Leprêtre S, Labussière-Wallet H, Nicolini F-E, et al. High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2014;49:664–70.

    Article  CAS  PubMed  Google Scholar 

  26. Silva Lde P, Patah PA, Saliba RM, Szewczyk NA, Gilman L, Neumann J. et al. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type. Haematologica. 2010;95:1183–90.

    Article  PubMed  Google Scholar 

  27. Ruggeri A, Roth-Guepin G, Battipaglia G, Mamez A-C, Malard F, Gomez A, et al. Incidence and risk factors for hemorrhagic cystitis in unmanipulated haploidentical transplant recipients. Transpl Infect Dis. 2015;17:822–30.

    Article  CAS  PubMed  Google Scholar 

  28. Girmenia C, Raiola AM, Piciocchi A, Algarotti A, Stanzani M, Cudillo L, et al. Incidence and outcome of invasive fungal diseases after allogeneic stem cell transplantation: a prospective study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO). Biol Blood Marrow Transplant. 2014;20:872–80.

    Article  PubMed  Google Scholar 

  29. Kontoyiannis DP, Marr KA, Park BJ, Alexander BD, Anaissie EJ, Walsh TJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–6: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database. Clin Infect Dis. 2010;50:1091–1100.

    Article  PubMed  Google Scholar 

  30. Robinson TM, O’Donnell PV, Fuchs EJ, Luznik L. Haploidentical bone marrow and stem cell transplantation: experience with post-transplantation cyclophosphamide. Semin Hematol. 2016;53:90–7.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Kanakry CG, Fuchs EJ, Luznik L. Modern approaches to HLA-haploidentical blood or marrow transplantation. Nat Rev Clin Oncol. 2016;13:10–24.

    Article  CAS  PubMed  Google Scholar 

  32. Montoro J, Sanz J, Sanz GF, Sanz MA. Advances in haploidentical stem cell transplantation for hematologic malignancies. Leuk Lymphoma. 2016;57:1766–75.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut de Cancérologie Lucien Neuwirth, Saint-Etienne, France

    Amandine Fayard, Elisabeth Daguenet & Jérôme Cornillon

  2. Institut Paoli Calmettes, Marseille, France

    Didier Blaise

  3. CHU Nantes, Nantes, France

    Patrice Chevallier

  4. Centre Hospitalier Lyon-Sud, Lyon, France

    Hélène Labussière

  5. CHRU Besançon, Besançon, France

    Ana Berceanu

  6. CHRU Lille, Lille, France

    Ibrahim Yakoub-Agha

  7. Hôpital Saint-Louis, Paris, France

    Gérard Socié & Régis Peffault de la Tour

  8. CHU Amiens, Amiens, France

    Amandine Charbonnier

  9. Hôpital Necker, Paris, France

    Felipe Suarez

  10. Institut Universitaire du Cancer, Toulouse, France

    Anne Huynh

  11. CHU Angers, Angers, France

    Mélanie Mercier

  12. CHU Grenoble, Grenoble, France

    Claude-Eric Bulabois

  13. CHU Hautepierre, Strasbourg, France

    Bruno Lioure

  14. Institut d’Hématologie Caen, Caen, France

    Sylvain Chantepie

  15. CHU Sart Tilman, Liège, Belgium

    Yves Beguin

  16. Centre Gustave Roussy, Villejuif, France

    Jean-Henri Bourhis

  17. Hôpital d’instruction des armées Percy, Paris, France

    Jean-Valère Malfuson

  18. Hôpital Universitaire, Bordeaux, France

    Laurence Clément

Authors
  1. Amandine Fayard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elisabeth Daguenet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Didier Blaise
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Patrice Chevallier
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hélène Labussière
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ana Berceanu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ibrahim Yakoub-Agha
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gérard Socié
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Amandine Charbonnier
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Felipe Suarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Anne Huynh
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Mélanie Mercier
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Claude-Eric Bulabois
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Bruno Lioure
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Sylvain Chantepie
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Yves Beguin
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Jean-Henri Bourhis
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Jean-Valère Malfuson
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Laurence Clément
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Régis Peffault de la Tour
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Jérôme Cornillon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jérôme Cornillon.

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

Fayard, A., Daguenet, E., Blaise, D. et al. Evaluation of infectious complications after haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide following reduced-intensity and myeloablative conditioning: a study on behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC). Bone Marrow Transplant 54, 1586–1594 (2019). https://doi.org/10.1038/s41409-019-0475-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-019-0475-7

This article is cited by

Search

Advanced search

Quick links