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.

  • Original Article
  • Published:

Infections

Fungal and viral infections after allogeneic hematopoietic transplantation from unrelated donors in adults: improving outcomes over time

Bone Marrow Transplantation volume 50, pages 274–281 (2015)Cite this article

Subjects

Abstract

Umbilical cord blood (CB) is increasingly used as an alternative source of stem cells in adult unrelated transplantation. Although registry studies report similar overall outcomes in comparison with BM/PB, comparative studies focusing on severe infections and infection-RM (IRM) with a long follow-up are scarce. A total of 434 consecutive unrelated transplants (1997–2009) were retrospectively analyzed to compare overall outcomes, incidence and risk factors of severe viral and invasive fungal infections in CB (n=65) vs BM/PB recipients (n=369). The 5-year OS was 38 vs 43%, respectively (P=0.2). CB transplantation (CBT) was associated with a higher risk of invasive aspergillosis (100-days-cumulative incidence 16 vs 6%, P=0.04) and CMV infection without differences in RM. No statistically significant differences were found regarding NRM (NRM of 38% in CB vs 37% in BM/PB at 1 year) nor IRM (30% in CB vs 27% in BM/PB at 1 year). In the overall population, NRM and IRM improved in more recent years. In adults who receive a single CBT, the risk of severe infections is increased when compared with unrelated BM/PB recipients, but mortality from infections is similar, leading to similar NRM and survival.

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

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. van Kraaij MG, Verdonck LF, Rozenberg-Arska M, Dekker AW . Early infections in adults undergoing matched related and matched unrelated/mismatched donor stem cell transplantation: a comparison of incidence. Bone Marrow Transplant 2002; 30: 303–309.

    Article  CAS  PubMed  Google Scholar 

  2. Williamson EC, Millar MR, Steward CG, Cornish JM, Foot AB, Oakhill A et al. Infections in adults undergoing unrelated donor bone marrow transplantation. Br J Haematol 1999; 104: 560–568.

    Article  CAS  PubMed  Google Scholar 

  3. Kim SH, Kee SY, Lee DG, Choi SM, Park SH, Kwon JC et al. Infectious complications following allogeneic stem cell transplantation: reduced-intensity vs myeloablative conditioning regimens. Transpl Infect Dis 2013; 15: 49–59.

    Article  PubMed  Google Scholar 

  4. Saavedra S, Jarque I, Sanz GF, Moscardó F, Jiménez C, Martín G et al. Infectious complications in patients undergoing unrelated donor bone marrow transplantation: experience from a single institution. Clin Microbiol Infect 2002; 8: 725–733.

    Article  CAS  PubMed  Google Scholar 

  5. Yoo JH, Lee DG, Choi SM, Choi JH, Park YH, Kim YJ et al. Infectious complications and outcomes after allogeneic hematopoietic stem cell transplantation in Korea. Bone Marrow Transplant 2004; 34: 497–504.

    Article  PubMed  Google Scholar 

  6. Ninin E, Milpied N, Moreau P, Andre-Richet B, Morineau N, Mahe B et al. Longitudinal study of bacterial, viral, and fungal infections in adult recipients of bone marrow transplants. Clin Infect Dis 2001; 33: 41–47.

    Article  CAS  PubMed  Google Scholar 

  7. Saavedra S, Sanz GF, Jarque I, Moscardó F, Jiménez C, Lorenzo I et al. Early infections in adult patients undergoing unrelated donor cord blood transplantation. Bone Marrow Transplant 2002; 30: 937–943.

    Article  CAS  PubMed  Google Scholar 

  8. Saber W, Opie S, Rizzo JD, Zhang MJ, Horowitz MM, Schriber J . Outcomes after matched unrelated donor vs identical sibling hematopoietic cell transplantation in adults with acute myelogenous leukemia. Blood 2012; 119: 3908–3916.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Horowitz MM . Does matched unrelated donor transplantation have the same outcome as matched sibling transplantation in unselected patients? Best Pract Res Clin Haematol 2012; 25: 483–486.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Barker JN, Byam C, Scaradavou A . How I treat: the selection and acquisition of unrelated cord blood grafts. Blood 2011; 117: 2332–2339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Barker JN, Davies SM, DeFor T, Ramsay NK, Weisdorf DJ, Wagner JE . Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched-pair analysis. Blood 2001; 97: 2957–2961.

    Article  CAS  PubMed  Google Scholar 

  12. Takahashi S, Iseki T, Ooi J, Tomonari A, Takasugi K, Shimohakamada Y et al. Single-institute comparative analysis of unrelated bone marrow transplantation and cord blood transplantation for adult patients with hematological malignancies. Blood 2004; 104: 3813–3820.

    Article  CAS  PubMed  Google Scholar 

  13. Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ, Champlin RE et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004; 351: 2265–2275.

    Article  CAS  PubMed  Google Scholar 

  14. Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A et al. Eurocord-Netcord Registry Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med 2004; 351: 2276–2285.

    Article  CAS  PubMed  Google Scholar 

  15. Atsuta Y, Suzuki R, Nagamura-Inoue T, Tanigushi S, Takahashi S, Kai S et al. Disease-specific analyses of unrelated cord blood transplantation compared with unrelated bone marrow transplantation in adult patients with acute leukemia. Blood 2009; 113: 1631–1638.

    Article  PubMed  Google Scholar 

  16. Parody R, Martino R, Rovira M, Vazquez L, Vázquez MJ, de la Cámara R et al. Severe infections after unrelated donor allogeneic hematopoietic stem cell transplantation in adults: comparison of cord blood transplantation with peripheral blood and bone marrow transplantation. Infectious/Non-infectious Complications Subcommittee of the Grupo Español de Trasplante Hematopoyético (GETH). Biol Blood Marrow Transplant 2006; 12: 734–748.

    Article  PubMed  Google Scholar 

  17. Sanz J, Boluda JC, Martín C, González M, Ferrá C, Serrano D et al. Single-unit umbilical cord blood transplantation from unrelated donors in patients with hematological malignancy using busulfan, thiotepa, fludarabine and ATG as myeloablative conditioning regimen. Bone Marrow Transplant 2012; 47: 1287–1293.

    Article  CAS  PubMed  Google Scholar 

  18. Bautista G, Cabrera JR, Regidor C, Forés R, García-Marco JA, Ojeda E et al. Cord blood transplants supported by co-infusion of mobilized hematopoietic stem cells from a third-party donor. Bone Marrow Transplant 2009; 43: 365–373.

    Article  CAS  PubMed  Google Scholar 

  19. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46: 1813–1821.

    Article  PubMed  Google Scholar 

  20. Ljungman P, Griffiths P, Paya C . Definitions of cytomegalovirus infections and disease in transplant recipients. Clin Infect Dis 2002; 34: 1094–1097.

    Article  PubMed  Google Scholar 

  21. Ogata M, Satou T, Kadota J, Saito N, Yoshida T, Okumura H et al. Human herpesvirus 6 (HHV-6) reactivation and HHV-6 encephalitis after allogeneic hematopoietic cell transplantation: a multicenter, prospective study. Clin Infect Dis 2013; 57: 671–681.

    Article  PubMed  Google Scholar 

  22. Reddy N, Rezvani K, Barrett AJ, Savani BN . Strategies to prevent EBV reactivation and posttransplant lymphoproliferative disorders (PTLD) after allogeneic stem cell transplantation in high-risk patients. Biol Blood Marrow Transplant 2011; 17: 591–597.

    Article  PubMed  Google Scholar 

  23. Cesaro S, Hirsch HH, Faraci M, Owoc-Lempach J, Beltrame A, Tendas A et al. European Group for Blood and Marrow Transplantation. Cidofovir for BK virus-associated hemorrhagic cystitis: a retrospective study. Clin Infect Dis 2009; 49: 233–240.

    Article  CAS  PubMed  Google Scholar 

  24. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. Consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  25. Sullivan KM, Agura E, Anasetti C, Appelbaum F, Badger C, Bearman S et al. Chronic graft-vs host disease and other late complications of bone marrow transplantation. Semin Hematol 1991; 28: 250–259.

    CAS  PubMed  Google Scholar 

  26. Klein JP, Rizzo JD, Zhang MJ, Keiding N . Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part I: unadjusted analysis. Bone Marrow Transplant 2001; 28: 909–915.

    Article  CAS  PubMed  Google Scholar 

  27. Klein JP, Rizzo JD, Zhang MJ, Keiding N . Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part 2: regression modeling. Bone Marrow Transplant 2001; 28: 1001–1011.

    Article  CAS  PubMed  Google Scholar 

  28. Iacobelli S EBMT Statistical Committee. Suggestions on the use of statistical methodologies in studies of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 2013; 48 (Suppl 1): S1–S37.

    Article  PubMed  Google Scholar 

  29. Boeckh M, Nichols WG . The impact of Cytomegalovirus serostatus of donor and recipient before allogeneic hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood 2004; 103: 2003–2008.

    Article  CAS  PubMed  Google Scholar 

  30. Mikulska M, Raiola AM, Bruzzi P, Varaldo R, Annunziata S, Lamparelli T et al. CMV infection after transplant from cord blood compared to other alternative donors: the importance of donor-negative CMV serostatus. Biol Blood Marrow Transplant 2012; 18: 92–99.

    Article  PubMed  Google Scholar 

  31. McCann S, Byrne JL, Rovira M, Shaw P, Ribaud P, Sica S et al. Outbreaks of infectious diseases in stem cell transplant units: a silent cause of death for patients and transplant programmes. Bone Marrow Transplant 2004; 33: 519–529.

    Article  CAS  PubMed  Google Scholar 

  32. Takahashi S, Ooi J, Tomonari A, Konuma T, Tsukada N, Oiwa-Monna M et al. Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. Blood 2007; 109: 1322–1330.

    Article  CAS  PubMed  Google Scholar 

  33. Yakushiji K, Gondo H, Kamezaki K, Shigematsu K, Hayashi S, Kuroiwa M et al. Monitoring of Cytomegalovirus reactivation after allogeneic stem cell transplantation: comparison of an antigenemia assay and quantitative real-time polimerase chain reaction. Bone Marrow Transplant 2002; 29: 599–606.

    Article  CAS  PubMed  Google Scholar 

  34. Garrigue I, Boucher S, Couzi L, Caumont A, Dromer C, Neau-Cransac M et al. Whole blood real-time quantitative PCR for cytomegalovirus infection follow-up in transplant recipients. J Clin Virol 2006; 36: 72–75.

    Article  CAS  PubMed  Google Scholar 

  35. Omar H, Hagglünd H, Gustavson-Jernberg A, LeBlanc K, Mattsson J, Remberger M et al. Targeted monitoring of patients at high risk of post-transplant lymphoproliferative disease by quantitative Epstein Barr virus polymerase chain reaction. Transplant Infect Dis 2009; 11: 393–399.

    Article  CAS  Google Scholar 

  36. Bacigalupo A, Sormani MP, Lamparelli T, Gualandi F, Occhini D, Bragante S et al. Reducing transplant-related mortality after allogeneic hematopoietic stem cell transplantation. Haematologica 2004; 89: 1238–1247.

    PubMed  Google Scholar 

  37. Martino R, Kerguelen A, Valcárcel D, Sureda A, Fachini L, Piñana JL et al. Reduction of infection-related mortality after allogeneic PBSCT from HLA identical siblings: longitudinal analysis from 1994 to 2008 at a single institution. Bone Marrow Transplant 2011; 46: 690–701.

    Article  CAS  PubMed  Google Scholar 

  38. Horan JT, Logan BR, Agovi-Johnson MA, Lazarus HM, Bacigalupo AA, Ballen KK et al. Reducing the risk for transplantation-related mortality after allogeneic hematopoietic cell transplantation: how much progress has been made? J Clin Oncol 2011; 29: 805–813.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kurosawa S, Yakushijin K, Yamaguchi T, Atsuta Y, Nagamura-Inoue Y, Akiyama H et al. Changes in incidence and causes of non-relapse mortality after allogeneic hematopoietic cell transplantation in patients with acute leukemia/myelodysplastic syndrome: an analysis of the Japan Transplant Outcome Registry. Bone Marrow Transplant 2013; 48: 529–536.

    Article  CAS  PubMed  Google Scholar 

  40. Sukdolak C, Tischer S, Dieks D, Figueiredo C, Goudeva L, Heuft HG et al. CMV-, EBV- and ADV-specific T cell immunity: screening and monitoring of potential third-party donors to improve post-transplantation outcome. Biol Blood Marrow Transplant 2013; 19: 1480–1492.

    Article  CAS  PubMed  Google Scholar 

  41. Fuji S, Kapp M, Grigoleit GU, Einsele H . Adoptive immunotherapy with virus-specific T cells. Best Pract Res Clin Haematol 2011; 24: 413–419.

    Article  CAS  PubMed  Google Scholar 

  42. Sanz GF, Saavedra S, Planelles D, Senent L, Cervera J, Barragán E et al. Standarised unrelated donor cord blood transplantation in adults with hematalogic malignancies. Blood 2001; 98: 2332–2338.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. R Parody and R Martino: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Clinical Hematology, Hospital Universitario Virgen del Rocío, Sevilla, Spain

    R Parody, F J Marquez-Malaver & I Espigado

  2. Division of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    R Martino, A Esquirol & I Garcia-Cadenas

  3. Division of Clinical Hematology, Hospital de la Princesa, Madrid, Spain

    R de la Cámara & A García-Noblejas

  4. Division of Clinical Hematology, Hospital Clínico Universitario de Salamanca, Barcelona, Spain

    T Villaescusa, D Caballero & L Vazquez

  5. Division of Clinical Hematology, Hospital Clínic i Provincial, Barcelona, Spain

    M Rovira & F Fernandez-Avilés

  6. Division of Clinical Hematology, Hospital Morales Meseguer, Murcia, Spain

    C Castilla-Llorente & I Heras

  7. Division of Clinical Hematology, Hospital Puerta del Hierro, Madrid, Spain

    M A Cabero & J R Cabrera

  8. Division of Clinical Hematology, Hospital Vall d’Hebron, Barcelona, Spain

    P Barba & D Valcarcel

  9. Division of Clinical Hematology, Hospital Duran i Reynalds, ICO, Barcelona, Spain

    I Sánchez-Ortega & R F Duarte

  10. Division of Clinical Hematology, Hospital Gregorio Marañón, Madrid, Spain

    D Serrano & F Carretero

Authors
  1. R Parody
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Martino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R de la Cámara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A García-Noblejas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Esquirol
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. I Garcia-Cadenas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T Villaescusa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D Caballero
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. M Rovira
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. F Fernandez-Avilés
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. F J Marquez-Malaver
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. I Espigado
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. C Castilla-Llorente
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. I Heras
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. M A Cabero
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. J R Cabrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. P Barba
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. D Valcarcel
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. I Sánchez-Ortega
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. R F Duarte
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. D Serrano
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. F Carretero
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. L Vazquez
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the Infectious/Non-infectious Complications Subcommittees of the Grupo Español de Trasplante Hematopoyético (GETH)

Corresponding author

Correspondence to R Parody.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Parody, R., Martino, R., de la Cámara, R. et al. Fungal and viral infections after allogeneic hematopoietic transplantation from unrelated donors in adults: improving outcomes over time. Bone Marrow Transplant 50, 274–281 (2015). https://doi.org/10.1038/bmt.2014.229

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2014.229

This article is cited by

Search

Advanced search

Quick links