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:

The impact of graft cell source on bloodstream infection in the first 100 days after allogeneic hematopoietic cell transplantation

Bone Marrow Transplantation volume 56, pages 1625–1634 (2021)Cite this article

Subjects

Abstract

Bloodstream infection (BSI) is a major infectious complication after allogeneic hematopoietic cell transplantation (HCT). To clarify the impact of graft cell source on the incidence of BSI after transplantation, we retrospectively examined 782 adult patients receiving their first allogeneic HCT: 122 recipients of related peripheral blood stem cells or bone marrow, 215 recipients of unrelated bone marrow, and 445 recipients of unrelated umbilical cord blood (U-CB). The cumulative incidence of BSI was 42.5% at 100 days after transplantation (95% confidence interval, 39.0–46.0). Gram-positive cocci were present in 64.2% of detected isolates. Among the pre-transplant factors including age, performance status, primary disease, disease status, graft cell source, sex and ABO blood type matching, and the intensity of conditioning regimen, U-CB use was identified as the most significant risk factor for BSI by multivariate analysis (hazard ratio, 1.76; 95% confidence interval, 1.40–2.22; p < 0.00001). Among the U-CB recipients, those who are not in remission at the time of transplantation were at the greatest risk of BSI (hazard ratio, 1.69; 95% confidence interval, 1.14–2.50; p < 0.01). The study makes it clear that graft cell source has an impact on BSI development after allogeneic HCT.

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: Cumulative incidence of bloodstream infection.
Fig. 2: Cumulative incidence of each Gram stain classification (A), and number of occurrences of each Gram stain classification by time series (B).

Similar content being viewed by others

References

  1. Collin BA, Leather HL, Wingard JR, Ramphal R. Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients. Clin Infect Dis. 2001;33:947–53.

    Article  CAS  Google Scholar 

  2. Ortega M, Rovira M, Almela M, Marco F, de la Bellacasa JP, Martinez JA, et al. Bacterial and fungal bloodstream isolates from 796 hematopoietic stem cell transplant recipients between 1991 and 2000. Ann Hematol. 2005;84:40–6.

    Article  Google Scholar 

  3. Almyroudis NG, Fuller A, Jakubowski A, Sepkowitz K, Jaffe D, Small TN, et al. Pre- and post-engraftment bloodstream infection rates and associated mortality in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2005;7:11–7.

    Article  CAS  Google Scholar 

  4. Parody R, Martino R, Rovira M, Vazquez L, Vazquez MJ, de la Camara 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. Biol Blood Marrow Transplant. 2006;12:734–48.

    Article  Google Scholar 

  5. Poutsiaka DD, Price LL, Ucuzian A, Chan GW, Miller KB, Snydman DR. Blood stream infection after hematopoietic stem cell transplantation is associated with increased mortality. Bone Marrow Transplant. 2007;40:63–70.

    Article  CAS  Google Scholar 

  6. Mikulska M, Del Bono V, Raiola AM, Bruno B, Gualandi F, Occhini D, et al. Blood stream infections in allogeneic hematopoietic stem cell transplant recipients: reemergence of Gram-negative rods and increasing antibiotic resistance. Biol Blood Marrow Transplant. 2009;15:47–53.

    Article  CAS  Google Scholar 

  7. Liu CY, Lai YC, Huang LJ, Yang YW, Chen TL, Hsiao LT, et al. Impact of bloodstream infections on outcome and the influence of prophylactic oral antibiotic regimens in allogeneic hematopoietic SCT recipients. Bone Marrow Transplant. 2011;46:1231–9.

    Article  CAS  Google Scholar 

  8. Busca A, Cavecchia I, Locatelli F, D’Ardia S, De Rosa FG, Marmont F, et al. Blood stream infections after allogeneic stem cell transplantation: a single-center experience with the use of levofloxacin prophylaxis. Transpl Infect Dis. 2012;14:40–8.

    Article  CAS  Google Scholar 

  9. Bock AM, Cao Q, Ferrieri P, Young JA, Weisdorf DJ. Bacteremia in blood or marrow transplantation patients: clinical risk factors for infection and emerging antibiotic resistance. Biol Blood Marrow Transplant. 2013;19:102–8.

    Article  Google Scholar 

  10. Gudiol C, Garcia-Vidal C, Arnan M, Sanchez-Ortega I, Patino B, Duarte R, et al. Etiology, clinical features and outcomes of pre-engraftment and post-engraftment bloodstream infection in hematopoietic SCT recipients. Bone Marrow Transplant. 2014;49:824–30.

    Article  CAS  Google Scholar 

  11. Blennow O, Ljungman P, Sparrelid E, Mattsson J, Remberger M. Incidence, risk factors, and outcome of bloodstream infections during the pre-engraftment phase in 521 allogeneic hematopoietic stem cell transplantations. Transpl Infect Dis. 2014;16:106–14.

    Article  CAS  Google Scholar 

  12. Kikuchi M, Akahoshi Y, Nakano H, Ugai T, Wada H, Yamasaki R, et al. Risk factors for pre- and post-engraftment bloodstream infections after allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis. 2015;17:56–65.

    Article  CAS  Google Scholar 

  13. Young JH, 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  Google Scholar 

  14. Ballen K, Woo Ahn K, Chen M, Abdel-Azim H, Ahmed I, Aljurf M, et al. Infection rates among acute leukemia patients receiving alternative donor hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22:1636–45.

    Article  Google Scholar 

  15. Saavedra S, Sanz GF, Jarque I, Moscardo F, Jimenez C, Lorenzo I, et al. Early infections in adult patients undergoing unrelated donor cord blood transplantation. Bone Marrow Transplant. 2002;30:937–43.

    Article  CAS  Google Scholar 

  16. Narimatsu H, Matsumura T, Kami M, Miyakoshi S, Kusumi E, Takagi S, et al. Bloodstream infection after umbilical cord blood transplantation using reduced-intensity stem cell transplantation for adult patients. Biol Blood Marrow Transplant. 2005;11:429–36.

    Article  Google Scholar 

  17. Tomonari A, Takahashi S, Ooi J, Tsukada N, Konuma T, Kobayashi T, et al. Bacterial bloodstream infection in neutropenic adult patients after myeloablative cord blood transplantation: experience of a single institution in Japan. Int J Hematol. 2007;85:238–41.

    Article  Google Scholar 

  18. Cahu X, Rialland F, Touzeau C, Chevallier P, Guillaume T, Delaunay J, et al. Infectious complications after unrelated umbilical cord blood transplantation in adult patients with hematologic malignancies. Biol Blood Marrow Transplant. 2009;15:1531–7.

    Article  Google Scholar 

  19. Yazaki M, Atsuta Y, Kato K, Kato S, Taniguchi S, Takahashi S, et al. Incidence and risk factors of early bacterial infections after unrelated cord blood transplantation. Biol Blood Marrow Transplant. 2009;15:439–46.

    Article  Google Scholar 

  20. Sanz J, Cano I, Gonzalez-Barbera EM, Arango M, Reyes J, Montesinos P, et al. Bloodstream infections in adult patients undergoing cord blood transplantation from unrelated donors after myeloablative conditioning regimen. Biol Blood Marrow Transplant. 2015;21:755–60.

    Article  Google Scholar 

  21. Zheng C, Tang B, Zhu X, Zhang X, Zhang L, Geng L, et al. Pre-engraftment bloodstream infections in acute leukemia patients undergoing unrelated cord blood transplantation following intensified myeloablative conditioning without ATG. Ann Hematol. 2017;96:115–24.

    Article  CAS  Google Scholar 

  22. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008;36:309–32.

    Article  Google Scholar 

  23. Dandoy CE, Ardura MI, Papanicolaou GA, Auletta JJ. Bacterial bloodstream infections in the allogeneic hematopoietic cell transplant patient: new considerations for a persistent nemesis. Bone Marrow Transplant. 2017;52:1091–106.

    Article  CAS  Google Scholar 

  24. Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002;34:730–51.

    Article  Google Scholar 

  25. Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011;52:e56–93.

    Article  Google Scholar 

  26. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628–33.

    Article  Google Scholar 

  27. Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15:367–9.

    Article  Google Scholar 

  28. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48:452–8.

    Article  CAS  Google Scholar 

  29. Dandoy CE, Kim S, Chen M, Ahn KW, Ardura MI, Brown V, et al. Incidence, risk factors, and outcomes of patients who develop mucosal barrier injury-laboratory confirmed bloodstream infections in the first 100 days after allogeneic hematopoietic stem cell transplant. JAMA Netw Open. 2020;3:e1918668.

    Article  Google Scholar 

  30. Ge J, Yang T, Zhang L, Zhang X, Zhu X, Tang B, et al. The incidence, risk factors and outcomes of early bloodstream infection in patients with malignant hematologic disease after unrelated cord blood transplantation: a retrospective study. BMC Infect Dis. 2018;18:654.

    Article  CAS  Google Scholar 

  31. Yanada M, Takami A, Yamasaki S, Arai Y, Konuma T, Uchida N, et al. Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia conducted in Japan during the past quarter century. Ann Hematol. 2020;99:1351–60.

    Article  Google Scholar 

  32. Bejanyan N, Brunstein CG, Cao Q, Lazaryan A, Luo X, Curtsinger J, et al. Delayed immune reconstitution after allogeneic transplantation increases the risks of mortality and chronic GVHD. Blood Adv. 2018;2:909–22.

    Article  CAS  Google Scholar 

  33. Schots R, Trullemans F, Van Riet I, Kaufman L, Hafsia A, Meddeb B, et al. The clinical impact of early gram-positive bacteremia and the use of vancomycin after allogeneic bone marrow transplantation. Transplantation. 2000;69:1511–4.

    Article  CAS  Google Scholar 

  34. Kimura S, Akahoshi Y, Nakano H, Ugai T, Wada H, Yamasaki R, et al. Antibiotic prophylaxis in hematopoietic stem cell transplantation. A meta-analysis of randomized controlled trials. J Infect. 2014;69:13–25.

    Article  Google Scholar 

  35. van Burik JA, Carter SL, Freifeld AG, High KP, Godder KT, Papanicolaou GA, et al. Higher risk of cytomegalovirus and aspergillus infections in recipients of T cell-depleted unrelated bone marrow: analysis of infectious complications in patients treated with T cell depletion versus immunosuppressive therapy to prevent graft-versus-host disease. Biol Blood Marrow Transplant. 2007;13:1487–98.

    Article  Google Scholar 

  36. Maung KK, Horwitz ME. Current and future perspectives on allogeneic transplantation using ex vivo expansion or manipulation of umbilical cord blood cells. Int J Hematol. 2019;110:50–8.

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank the patients and the donors. We also thank physicians, nurses, pharmacists, transplantation coordinator (Ms. Madoka Narita), data managers (Ms. Rumiko Tsuchihashi and Ms. Kaori Kobayashi), other co-medical staffs, and support personnel for their care of the patients involved in the study.

Author information

Authors and Affiliations

  1. Department of Hematology, Toranomon Hospital, Tokyo, Japan

    Shinsuke Takagi, Naoyuki Uchida, Mitsuhiro Yuasa, Kosei Kageyama, Daisuke Kaji, Yuki Taya, Hisashi Yamamoto, Go Yamamoto, Yuki Asano-Mori, Koji Izutsu & Shuichi Taniguchi

  2. Department of Infectious Diseases, Toranomon Hospital, Tokyo, Japan

    Sho Ogura, Hideki Araoka, Muneyoshi Kimura & Akiko Yoneyama

  3. Department of Hematology, Toranomon Hospital Kajigaya, Kanagawa, Japan

    Takashi Mitsuki, Aya Nishida, Kazuya Ishiwata & Atsushi Wake

  4. Department of Clinical Laboratory, Toranomon Hospital, Tokyo, Japan

    Yukako Koike & Akiko Yoneyama

  5. Department of Transfusion Medicine, Toranomon Hospital, Tokyo, Japan

    Shigeyoshi Makino

  6. Okinaka Memorial Institute for Medical Research, Tokyo, Japan

    Shuichi Taniguchi

Authors
  1. Shinsuke Takagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sho Ogura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hideki Araoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Naoyuki Uchida
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takashi Mitsuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mitsuhiro Yuasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kosei Kageyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Daisuke Kaji
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuki Taya
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Aya Nishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Muneyoshi Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Kazuya Ishiwata
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hisashi Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Go Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Yuki Asano-Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Yukako Koike
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Koji Izutsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Atsushi Wake
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Shigeyoshi Makino
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Akiko Yoneyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Shuichi Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S. Takagi is the principal investigator and takes primary responsibility for the paper; S. Takagi wrote the manuscript; S. Takagi, NU, TM, MY, KK, DK, YT, AN, K. Ishiwata., H.Y., G.Y., Y.A-M, K. Izutsu., AW and S. Taniguchi treated patients and reviewed the final manuscript; SO, HA, MK, YK and SM reviewed the final manuscript; S. Takagi, AY, and S. Taniguchi designed the research; AY and S. Taniguchi organized the project.

Corresponding author

Correspondence to Shinsuke Takagi.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

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

Takagi, S., Ogura, S., Araoka, H. et al. The impact of graft cell source on bloodstream infection in the first 100 days after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 56, 1625–1634 (2021). https://doi.org/10.1038/s41409-021-01229-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-021-01229-6

This article is cited by

Search

Advanced search

Quick links