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Pre-engraftment bloodstream infections in acute leukemia patients undergoing unrelated cord blood transplantation following intensified myeloablative conditioning without ATG

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Abstract

The aim of this study is to investigate the impact of pre-engraftment bloodstream infections (BSIs) on the outcomes in acute leukemia patients undergoing myeloablative cord blood transplantation (CBT). A total of 226 acute leukemia patients who received unrelated CBT were enrolled in this study, and all these patients received an intensified myeloablative conditioning without ATG. Pre-engraftment BSIs occurred in 72 patients (31.9 %), and the median time of onset was 4.5 days after cord blood infusion, BSIs of gram-negative bacilli, and gram-positive cocci comprised of 63.8 and 36.2 %, respectively. The cumulative incidences of neutrophil and platelet engraftment, acute or chronic graft versus host disease (GVHD) were comparable among the non-BSI, gram-negative bacilli BSI, and gram-positive cocci BSI groups. The cumulative incidence of transplant-related mortality (TRM), relapse, overall survival (OS), and disease-free survival (DFS) was similar between the non-BSI and the BSI groups. For subgroups analysis, TRM was lower in gram-positive cocci BSI patients compared with that of gram-negative bacilli BSI patients (8.3 vs 39.3 %) (p = 0.01) (HR = 0.39, p = 0.034), and the 5-year OS was higher in gram-positive cocci BSI cohort (79.1 vs 44.2 %) (p = 0.01) (HR = 0.36, p = 0.046). Our study demonstrated that, for acute leukemia patients who received CBT after myeloablative conditioning that omitted ATG, pre-engraftment BSI had no impact on engraftment, GVHD, TRM, relapse, and long-term survival. Due to the fact that gram-negative bacilli BSI was associated with poor outcomes compared with gram-positive cocci BSI, appropriate early empirical antimicrobial management strategies and better supportive care are required to decrease the gram-negative bacilli BSI-related mortality.

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References

  1. Mohty M, Gaugler B (2010) Advances in umbilical cord transplantation: the role of thymoglobulin/ATG in cord blood transplantation. Best Pract Res Clin Haematol 23:275–282

    Article  CAS  PubMed  Google Scholar 

  2. Yazaki M, Atsuta Y, Kato K et al (2009) Japan Cord Blood Bank Network. Incidence and risk factors of early bacterial infections after unrelated cord blood transplantation. Biol Blood Marrow Transplant 15:439–446

    Article  PubMed  Google Scholar 

  3. Tomonari A, Takahashi S, Ooi J et al (2007) Bacterial bloodstream infection in neutropenic adult patients after myeloablative cord blood transplantation: experience of a single institution in Japan. Int J Hematol 85:238–441

    Article  PubMed  Google Scholar 

  4. Narimatsu H, Matsumura T, Kami M et al (2005) Bloodstream infection after umbilical cord blood transplantation using reduced-intensity stem cell transplantation for adult patients. Biol Blood Marrow Transplant 11:429–436

    Article  PubMed  Google Scholar 

  5. Sanz J, Cano I, González-Barberá EM et al (2015) Bloodstream infections in adult patients undergoing cord blood transplantation from unrelated donors after myeloablative conditioning regimen. Biol Blood Marrow Transplant 21:755–760

    Article  PubMed  Google Scholar 

  6. Zheng C, Luan Z, Fang J et al (2015) Comparison of conditioning regimens with or without antithymocyte globulin for unrelated cord blood transplantation in children with high-risk or advanced hematological malignancies. Biol Blood Marrow Transplant 21:707–712

    Article  PubMed  Google Scholar 

  7. Zheng C, Zhu X, Tang B et al (2015) Comparative analysis of unrelated cord blood transplantation and HLA-matched sibling hematopoietic stem cell transplantation in children with high-risk or advanced acute leukemia. Ann Hematol 94:473–480

    Article  CAS  PubMed  Google Scholar 

  8. Park M, Lee SH, Lee YH et al (2013) Korean Cord Blood Transplantation Working Party. Pre-engraftment syndrome after unrelated cord blood transplantation: a predictor of engraftment and acute graft-versus-host disease. Biol Blood Marrow Transplant 19:640–646

    Article  PubMed  Google Scholar 

  9. Dignan FL, Clark A, Amrolia P et al (2012) Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. Diagnosis and management of acute graft-versus-host disease. Br J Haematol 158:30–45

    Article  CAS  PubMed  Google Scholar 

  10. Dignan FL, Amrolia P, Clark A et al (2012) Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol 158:46–61

    Article  CAS  PubMed  Google Scholar 

  11. Garg S, Wang W, Prabath BG et al (2014) Bone marrow transplantation helps restore the intestinal mucosal barrier after total body irradiation in mice. Radiat Res 181:229–239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang J, Shao L, Hendrickson HP et al (2015) Total Body Irradiation in the “Hematopoietic” Dose Range Induces Substantial Intestinal Injury in Non-Human Primates. Radiat Res 184:545–553

    Article  CAS  PubMed  Google Scholar 

  13. Almyroudis NG, Fuller A, Jakubowski A et al (2005) Pre- and post-engraftment bloodstream infection rates and associated mortality in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis 7:11–7

    Article  CAS  PubMed  Google Scholar 

  14. Sarashina T, Yoshida M, Iguchi A et al (2013) Risk factor analysis of bloodstream infection in pediatric patients after hematopoietic stem cell transplantation. J Pediatr Hematol Oncol 35:76–80

    Article  PubMed  Google Scholar 

  15. Kikuchi M, Akahoshi Y, Nakano H et al (2015) Risk factors for pre- and post-engraftment bloodstream infections after allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis 17:56–65

    Article  CAS  PubMed  Google Scholar 

  16. Gudiol C, Garcia-Vidal C, Arnan M et al (2014) Etiology, clinical features and outcomes of pre-engraftment and post-engraftment bloodstream infection in hematopoietic SCT recipients. Bone Marrow Transplant 49:824–830

    Article  CAS  PubMed  Google Scholar 

  17. Pascal L, Mohty M, Ruggeri A et al (2015) Impact of rabbit ATG-containing myeloablative conditioning regimens on the outcome of patients undergoing unrelated single-unit cord blood transplantation for hematological malignancies. Bone Marrow Transplant 50:45–50

    Article  CAS  PubMed  Google Scholar 

  18. Pascal L, Tucunduva L, Ruggeri A et al (2015) Eurocord and the European Society for Blood and Marrow Transplantation. Impact of ATG-containing reduced-intensity conditioning after single- or double-unit allogeneic cord blood transplantation. Blood 126:1027–1032

    Article  CAS  PubMed  Google Scholar 

  19. Baron F, Labopin M, Ruggeri A et al (2015) Unrelated cord blood transplantation for adult patients with acute myeloid leukemia: higher incidence of acute graft-versus-host disease and lower survival in male patients transplanted with female unrelated cord blood--a report from Eurocord, the Acute Leukemia Working Party, and the Cord Blood Committee of the Cellular Therapy and Immunobiology Working Party of the European Group for Blood and Marrow Transplantation. J Hematol Oncol 8:107

    Article  PubMed  PubMed Central  Google Scholar 

  20. Finke J, Bethge WA, Schmoor C, ATG-Fresenius Trial Group et al (2009) 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 10:855–864

    Article  CAS  PubMed  Google Scholar 

  21. Lindemans CA, Chiesa R, Amrolia PJ et al (2014) Impact of thymoglobulin prior to pediatric unrelated umbilical cord blood transplantation on immune reconstitution and clinical outcome. Blood 123:126–132

    Article  CAS  PubMed  Google Scholar 

  22. Averbuch D, Cordonnier C, Livermore DM et al (2013) ECIL4, a joint venture of EBMT, EORTC, ICHS, ESGICH/ESCMID and ELN. Targeted therapy against multi-resistant bacteria in leukemic and hematopoietic stem cell transplant recipients: guidelines of the 4th European Conference on Infections in Leukemia (ECIL-4, 2011). Haematologica 98:1836–1847

    Article  PubMed  PubMed Central  Google Scholar 

  23. Jaffe D, Jakubowski A, Sepkowitz K et al (2004) Prevention of peritransplantation viridans streptococcal bacteremia with early vancomycin administration: a single-center observational cohort study. Clin Infect Dis 39:1625–1632

    Article  CAS  PubMed  Google Scholar 

  24. Schots R, Trullemans F, Van Riet I et al (2000) The clinical impact of early gram-positive bacteremia and the use of vancomycin after allogeneic bone marrow transplantation. Transplantation 69:1511–1514

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81570159 and 81470350), Anhui Provincial Natural Science Foundation of China (No. 1608085MH181), and Anhui Provincial Public welfare Technology Application Research linkage project in 2015 (No. 1501ld04020).

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Correspondence to Zimin Sun.

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The authors declare that they have no conflict of interest.

Informed consent was obtained from all patients for being included in the study.

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Zheng, C., Tang, B., Zhu, X. et al. Pre-engraftment bloodstream infections in acute leukemia patients undergoing unrelated cord blood transplantation following intensified myeloablative conditioning without ATG. Ann Hematol 96, 115–124 (2017). https://doi.org/10.1007/s00277-016-2828-2

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  • DOI: https://doi.org/10.1007/s00277-016-2828-2

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