Skip to main content

Advertisement

SpringerLink
Log in

G-CSF-primed haplo-identical HSCT with intensive immunosuppressive and myelosuppressive treatments does not increase the risk of pre-engraftment bloodstream infection: a multicenter case–control study

  • Original Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

A multicenter retrospective study in 131 patients (44 females/87 males) with hematological disorders who underwent G-CSF-primed/haplo-identical (Haplo-ID) (n = 76) or HLA-identical (HLA-ID) HSCT (n = 55) from February 2013 to February 2016 was conducted to compare the incidence and risk factors for pre-engraftment bloodstream infection (PE-BSI). In the Haplo-ID group, 71/76 patients with high-risk (n = 28) or relapsed/refractory hematological malignancies (n = 43) received FA5-BUCY conditioning (NCT02328950). All received trimethoprim–sulfamethoxazole (TMP–SMX) prophylaxis. Blood cultures and catheter tip cultures were obtained to confirm the BSI. PE-BSI was detected in 24/131 HSCT patients (18/76 in Haplo-ID and 6/55 in HLA-ID) after 28 febrile neutropenic episodes. Among 28 isolates for the 24 patients, 21 (75%) were Gneg bacteria, 6 (21.4%) Gpos and 1 (3.6%) fungi. Bacteria sources were central venous line infection (7/29.2%), gastroenteritis (6/25%), lower respiratory tract infection (LRTI; 5/20.8%), perianal skin infection (4/16.7%), and unknown (2/8.3%). The duration of neutropenia (P = 0.046) and previous Gneg bacteremia (P = 0.037) were important risk factors by univariate analysis, while the type of HSCT was not. A trend of TMP–SMX-resistant BSI in both groups may be due to routine antibacterial prophylaxis strategies. Our data show that G-CSF-primed Haplo-ID HSCT did not increase the risk of PE-BSI, even with intensive immunosuppressive treatments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Poutsiaka DD, Munson D, Price LL, Chan GW, Snydman DR (2011) Blood stream infection (BSI) and acute GVHD after hematopoietic SCT (HSCT) are associated. Bone Marrow Transplant 46:300–307

    Article  CAS  PubMed  Google Scholar 

  2. Blennow O, Mattsson J, Remberger M (2013) Pre-engraftment blood stream infection is a risk factor for acute GVHD grades II–IV. Bone Marrow Transplant 48(12):1583–1584

    Article  CAS  PubMed  Google Scholar 

  3. Mikulska M, Del Bono V, Raiola AM et al (2009) Blood stream infections in allogeneic hematopoietic stem cell transplant recipients: reemergence of Gram-negative rods and increasing antibiotic resistance. Biol Blood Marrow Transplant 15:47–53

    Article  CAS  PubMed  Google Scholar 

  4. Almyroudis NG, Fuller A, Jakubowski A, Sepkowitz K, Jaffe D, Small TN et al (2005) Pre- and post-engraftment bloodstream infection rates and associated mortality in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis 7:11–17

    Article  CAS  PubMed  Google Scholar 

  5. Gudiol C, Garcia-Vidal C, Arnan M, Sánchez-Ortega I, Patiño B, Duarte R, Carratalà J (2014) Etiology, clinical features and outcomes of pre-engraftment and post-engraftment bloodstream infection in hematopoietic SCT recipients. Bone Marrow Transplant 49(6):824–830

    Article  CAS  PubMed  Google Scholar 

  6. Hong J, Moon SM, Ahn HK, Sym SJ, Park YS, Park J, Cho YK, Cho EK, Shin DB, Lee JH (2013) Comparison of characteristics of bacterial bloodstream infection between adult patients with allogeneic and autologous hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 19(6):994–999

    Article  PubMed  Google Scholar 

  7. Meyer E, Beyersmann J, Bertz H et al (2007) Risk factor analysis of blood stream infection and pneumonia in neutropenic patients after peripheral blood stem-cell transplantation. Bone Marrow Transplant 39:173–178

    Article  CAS  PubMed  Google Scholar 

  8. Busca A, Cavecchia I, Locatelli F, D'Ardia S, De Rosa FG, Marmont F, Ciccone G, Baldi I, Serra R, Gaido E, Falda M (2012) Blood stream infections after allogeneic stem cell transplantation: a single-center experience with the use of levofloxacin prophylaxis. Transpl Infect Dis 14(1):40–48

    Article  CAS  PubMed  Google Scholar 

  9. Parody R, Martino R, Rovira R et al (2006) 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 12:734–748

    Article  PubMed  Google Scholar 

  10. Blennow O, Ljungman P, Sparrelid E, Mattsson J, Remberger M (2014) Incidence, risk factors, and outcome of bloodstream infections during the pre-engraftment phase in 521 allogeneic hematopoietic stem cell transplantations. Transpl Infect Dis 16(1):106–114

    Article  CAS  PubMed  Google Scholar 

  11. Marena C, Zecca M, Carenini ML, Bruschi A, Bassi ML, Olivieri P, Azzaretti S, Locatelli F (2001) Incidence of, and risk factors for, nosocomial infections among hematopoietic stem cell transplantation recipients, with impact on procedure-related mortality. Infect Control Hosp Epidemiol 22(8):510–517

    Article  CAS  PubMed  Google Scholar 

  12. Junghanss C, Marr KA, Carter RA et al (2002) Incidence and outcome of bacterial and fungal infections following nonmyeloablative compared with myeloablative allogeneic hematopoietic stem cell transplantation: a matched control study. Biol Blood Marrow Transplant 8:512–520

    Article  PubMed  Google Scholar 

  13. Meunier F, Lukan C (2008) The first European Conference on Infections in Leukaemia - ECIL1: a current perspective. Eur J Cancer 44:2112–2117

    Article  PubMed  Google Scholar 

  14. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, Wingard JR, Young JA, Boeckh MJ (2009) Guidelines for preventing infectious complications among hematopoietic cell transplantationrecipients: a global perspective. Biol Blood Marrow Transplant 15:1143–1238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Center for International Blood and Marrow Transplant Research (CIBMTR); National Marrow Donor Program (NMDP); European Blood and Marrow Transplant Group (EBMT); American Society of Blood and Marrow Transplantation (ASBMT); Canadian Blood and Marrow Transplant Group (CBMTG); Infectious Disease Society of America (IDSA); Society for Healthcare Epidemiology of America (SHEA); Association of Medical Microbiology and Infectious Diseases Canada (AMMI); Centers for Disease Control and Prevention (CDC) (2009) Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective. Bone Marrow Transplant 44(8):453–558

    Article  Google Scholar 

  16. Yokoe D, Casper C, Dubberke E, Lee G, Muñoz P, Palmore T, Sepkowitz K, Young JA, Donnelly JP, Center for International Blood and Marrow Transplant Research; National Marrow Donor Program; European Blood and Marrow Transplant Group; American Society of Blood and Marrow Transplantation; Canadian Blood and Marrow Transplant Group; Infectious Disease Society of America; Society for Healthcare Epidemiology of America; Association of Medical Microbiology and Infectious Diseases Canada; Centers for Disease Control and Prevention (2009) Infection prevention and control in health-care facilities in which hematopoietic cell transplant recipients are treated. Bone Marrow Transplant 44(8):495–507

    Article  CAS  PubMed  Google Scholar 

  17. Xu LP, Chen H, Chen J et al (2018) The consensus on indications, conditioning regimen, and donor selection of allogeneic hematopoietic cell transplantation for hematological diseases in China-recommendations from the Chinese Society of Hematology. J Hematol Oncol 11(1):33

    Article  PubMed  PubMed Central  Google Scholar 

  18. Network N C C. Genetic/familial high-risk assessment: breast and ovarian[J]. NCCN Clinical Practice

  19. Cheson BD, Fisher RI, Barrington SF et al (2014) Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 32(27):3059–3068

    Article  PubMed  PubMed Central  Google Scholar 

  20. Tachibana T, Tanaka M, Takasaki H et al (2011) Pretransplant serum ferritin is associated with bloodstream infections within 100 days of allogeneic stem cell transplantation for myeloid malignancies. Int J Hematol 93(3):368–374

    Article  CAS  PubMed  Google Scholar 

  21. Kanda J, Mizumoto C, Ichinohe T et al (2011) Pretransplant serum ferritin and C-reactive protein as predictive factors for early bacterial infection after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 46:208–216

    Article  CAS  PubMed  Google Scholar 

  22. Wang Y, Liu Q-F, Xu L-P et al (2015) Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood 125(25):3956–3962

    Article  CAS  PubMed  Google Scholar 

  23. Gratwohl A (2012) The EBMT risk score. Bone Marrow Transplant 47(6):749–756

    Article  CAS  PubMed  Google Scholar 

  24. Yang T, Lin Q, Ren J, Chen P, Yuan X, Luo X, Liu T, Zheng J, Zheng Z, Zheng X, Chen X, Zhang L, Zheng H, Chen Z, Hua X, Le S, Li J, Chen Z, Hu J (2016) A 5-day cytoreductive chemotherapy followed by haplo-identical hsct (FA5-BUCY) as a tumor-ablative regimen improved the survival of patients with advanced hematological malignancies. Oncotarget 7(48):78773–78786

    PubMed  PubMed Central  Google Scholar 

  25. Al-Zahrani H, Nassar A, Al-Mohareb F, Al-Sharif F, Mohamed S, Al-Anazi K, Patel M, Rasheed W, Saleh AJ, Bakr M, Ahmed S, Ibrahim K, Hussain F, Elkum N, Elhassan T, Nurgat Z, Chaudhri N, Aljurf M (2011) Fludarabine-based conditioning chemotherapy for allogeneic hematopoietic stem cell transplantation in acquired severe aplastic anemia. Biol Blood Marrow Transplant 17(5):717–722

    Article  CAS  PubMed  Google Scholar 

  26. Kim H, Lee JH, Joo YD, Bae SH, Hyun MS, Lee JH, Kim DY, Lee WS, Ryoo HM, Kim MK, Park JH, Lee KH, Cooperative Study Group A for Hematology (COSAH) (2012) A randomized comparison of cyclophosphamide vs. reduced dose cyclophosphamide plus fludarabine for allogeneic hematopoietic cell transplantation in patients with aplastic anemia and hypoplastic myelodysplastic syndrome. Ann Hematol 91(9):1459–1469

    Article  CAS  PubMed  Google Scholar 

  27. Marks R, Potthoff K, Hahn J, Ihorst G, Bertz H, Spyridonidis A, Holler E, Finke JM (2008) Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies. Blood 112(2):415–425

    Article  CAS  PubMed  Google Scholar 

  28. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, Lerner KG, Thomas ED (1974) Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 18(4):295–304

    Article  CAS  PubMed  Google Scholar 

  29. Lee SJ, Vogelsang G, Flowers ME (2003) Chronic graft-versus-host disease. Biol Blood Marrow Transplant 9(4):215–233

    Article  CAS  PubMed  Google Scholar 

  30. Bader P, Beck J, Frey A et al (1998) Serial and quantitative analysis of mixed hematopoietic chimerism by PCR in patients with acute leukemias allows the prediction of relapse after allogeneic BMT. Bone Marrow Transplant 21(5):487–495

    Article  CAS  PubMed  Google Scholar 

  31. Horan T, Gaynes R (2004) Surveillance of nosocomial infections. In: Hospital epidemiology and infection control, 3rd edn. Philadelphia, Lippincott, Williams & Wilkeins, pp 1659–1702

    Google Scholar 

  32. DesJardin JA, Falagas ME, Ruthazer R, Griffith J, Wawrose D, Schenkein D et al (1999) Clinical utility of blood cultures drawn from indwelling central venous catheters in hospitalized patients with cancer. Ann Intern Med 131(9):641–647

    Article  CAS  PubMed  Google Scholar 

  33. Chinese Society of Hematology, Chinese Medical Association (2012) Chinese guidelines for the clinical application of antibacterial drugs for agranulocytosis with fever. Zhonghua Xue Ye Xue Za Zhi 33(8):693–696

    Google Scholar 

  34. Chinese Society of Hematology, Chinese Medical Association; Chinese Medical Doctor Association, Hematology Branch (2016) Chinese guidelines for the clinical application of antibacterial drugs for agranulocytosis with fever (2016). Zhonghua Xue Ye Xue Za Zhi 37(5):353–359

    Google Scholar 

  35. Averbuch D, Orasch C, Cordonnier C, Livermore DM, Mikulska M, Viscoli C, Gyssens IC, Kern WV, Klyasova G, Marchetti O, Engelhard D, Akova M, ECIL4, a joint venture of EBMT, EORTC, ICHS, ESGICH/ESCMID and ELN (2013) European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European conference on infections in leukemia. Haematologica 98(12):1826–1835

    Article  PubMed  PubMed Central  Google Scholar 

  36. Averbuch D, Cordonnier C, Livermore DM, Mikulska M, Orasch C, Viscoli C, Gyssens IC, Kern WV, Klyasova G, Marchetti O, Engelhard D, Akova M, ECIL4, a joint venture of EBMT, EORTC, ICHS, ESGICH/ESCMID and ELN (2013) 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(12):1836–1847

    Article  PubMed  PubMed Central  Google Scholar 

  37. Poutsiaka DD, Price LL, Ucuzian A, Chan GW, Miller KB, Snydman DR (2007) Blood stream infection after hematopoietic stem cell transplantation is associated with increased mortality. Bone Marrow Transplant 40(1):63–70

    Article  CAS  PubMed  Google Scholar 

  38. Huang XJ, Liu DH, Liu KY et al (2006) Haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of hematological malignancies. Bone Marrow Transplant 38:291–297

    Article  PubMed  Google Scholar 

  39. Tang W, Fan X, Wang L, Hu J (2015) Busulfan and fludarabine conditioning regimen given at hematological nadir of cytoreduction fludarabine, cytarabine, and idarubicin chemotherapy in patients with refractory acute myeloid leukemia undergoing allogeneic stem cell transplantation: a single arm pilot consort study. Medicine 94(15):e706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Johansson JE, Brune M, Ekman T. (2001) The gut mucosa barrier is preserved during allogeneic, haemopoietic stem cell transplantation with reduced intensity conditioning[J]. Bone marrow transplantation 28(8):737

  41. Niscola P, Romani C, Cupelli L et al (2007) Mucositis in patients with hematologic malignancies: an overview. Haematologica 92(2):222–231

    Article  PubMed  Google Scholar 

  42. Oliveira AL, de Souza M, Carvalho-Dias VM et al (2007) Epidemiology of bacteremia and factors associated with multi-drug-resistant gram-negative bacteremia in hematopoietic stem cell transplant recipients. Bone Marrow Transplant 39:775–781

    Article  CAS  PubMed  Google Scholar 

  43. Mikulska M, Del Bono V, Raiola AM, Bruno B, Gualandi F, Occhini D et al (2009) Bloodstream infections in allo-geneic hematopoietic stem cell transplant recipients: re-emergence of gram-negative rods and increasing antibiotic resistance. Biol Blood Marrow Transplant 15:47–53

    Article  CAS  PubMed  Google Scholar 

  44. Therriault BL, Wilson JW, Barreto JN, Estes LL (2010) Characterization of bacterial infection in allogenic hematopoietic stem cell transplant recipients who received prophylactic levofloxacin with either penicillin or doxacycline. Mayo Clin Proc 85(8):711–816

    Article  PubMed  PubMed Central  Google Scholar 

  45. Liu CY, Lai YC, Huang LJ, Yang YW, Chen TL, Hsiao LT et al (2011) Impact of bloodstream infections on outcome and the influence of prophylactic oral antibiotic regimens in allogeneic hematopoietic SCT recipients. Bone Marrow Transplant 46:1231–1239

    Article  CAS  PubMed  Google Scholar 

  46. El-Mahallawy H, Samir I, Abdel Fattah R, Kadry D, El-Kholy A (2014) Source, pattern and antibiotic resistance of blood stream infections in hematopoietic stem cell transplant recipients. J Egypt Natl Canc Inst 26(2):73–77

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by the National and Fujian Provincial Key Clinical Specialty Discipline Construction Program, China; National High Technology Research and Development Program of China; 863 program (2012AA02A505); National Public Health Grand Research Foundation (201202017); National Natural Science Foundation of China (81570162, 81700131, 81870138); Fujian Provincial Key Laboratory Foundation of Hematology (2009J1004); and Natural Science Foundation of Fujian Province (2017Y9017, 2017Y9037, 2017Y9056, 2018Y0031). The authors would like to thank all the nurses and physicians at the center who all contributed to the management of patient care, and Dr. Martine Torres for her critical reading of the manuscript and editorial assistance.

Author information

Author notes

  1. Jinhua Ren, Qiaoxian Lin, Weimin Chen and Congmeng Lin contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, 350001, Fuzhou, Fujian, People’s Republic of China

    Jinhua Ren, Qiaoxian Lin, Yuxin Zhang, Shaozhen Chen, Xiaohong Yuan, Ping Chen, Xiaofeng Luo, Qiuru Chen, Min Xiao, Yongquan Chen, Xueqiong Wu, Yanling Zeng, Zhizhe Chen, Jianda Hu & Ting Yang

  2. Department of Hematology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, Fujian, People’s Republic of China

    Qiaoxian Lin

  3. Department of Hematology, Fujian Provincial Hospital, Fuzhou, 350001, Fujian, People’s Republic of China

    Weimin Chen & Yun Lin

  4. Department of Hematology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, 363000, Fujian, People’s Republic of China

    Congmeng Lin, Lvying Shen, Mengxian Guo & Xudong Ma

  5. Department of Intensive Care Unit, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People’s Republic of China

    Cunrong Chen

  6. Department of Hematology, Affiliated Nanping First Hospital of Fujian Medical University, Nanping, 353000, Fujian, People’s Republic of China

    Yanling Zeng

Authors
  1. Jinhua Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiaoxian Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Weimin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Congmeng Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuxin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cunrong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shaozhen Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaohong Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ping Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xiaofeng Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yun Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Lvying Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Mengxian Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Qiuru Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Min Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Yongquan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Xueqiong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Yanling Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Zhizhe Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Xudong Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Jianda Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Ting Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Prof. Jianda Hu and Prof. Ting Yang designed and performed the research. Dr. Jinhua Ren and Dr. Qiaoxian Ling collected the data. Dr. Qiaoxian Ling performed the statistical analyses. Prof. Ting Yang interpreted the data and wrote the manuscript. All authors participated in the management of patient care. All authors critically reviewed and approved the manuscript.

Corresponding author

Correspondence to Ting Yang.

Ethics declarations

This study was conducted in accordance with the ethical standards of the local institutional review board (the Medical Ethics Committee of Fujian Medical University Union Hospital and the Helsinki Declaration). Informed consent was obtained from all patients and donors before they were included in the study.

Conflict of interest

The authors declare that they have no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ren, J., Lin, Q., Chen, W. et al. G-CSF-primed haplo-identical HSCT with intensive immunosuppressive and myelosuppressive treatments does not increase the risk of pre-engraftment bloodstream infection: a multicenter case–control study. Eur J Clin Microbiol Infect Dis 38, 865–876 (2019). https://doi.org/10.1007/s10096-019-03482-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-019-03482-6

Keywords

Search

Navigation