Bacterial blood stream infections (BSIs), particularly post-engraftment BSIs, are associated with increased mortality after allogeneic hematopoietic cell transplantation

Celalettin Ustun¹, Jo-Anne H Young², Genovefa A Papanicolaou³, Soyoung Kim^{4

5}, Kwang Woo Ahn^{4

5}, Min Chen⁴, Hisham Abdel-Azim⁶, Mahmoud Aljurf⁷, Amer Beitinjaneh⁸, Valerie Brown⁹, Jan Cerny¹⁰, Saurabh Chhabra¹¹, Mohamed A Kharfan-Dabaja¹², Parastoo B Dahi¹³, Andrew Daly¹⁴, Christopher E Dandoy¹⁵, Christopher C Dvorak¹⁶, Cesar O Freytes¹⁷, Shahrukh Hashmi^{7

18}, Hillard Lazarus¹⁹, Per Ljungman²⁰, Taiga Nishihori²¹, Kristin Page²², Sai R K Pingali²³, Ayman Saad²⁴, Bipin N Savani²⁵, Daniel Weisdorf²⁶, Kirsten Williams²⁷, Baldeep Wirk²⁸, Jeffery J Auletta²⁹, Caroline A Lindemans^{30

31}, Krishna Komanduri⁸, Marcie Riches³²

Affiliations

¹ Division of Hematology, Oncology and Cellular Therapy, Rush University, Chicago, IL, USA. Celalettin_Ustun@rush.edu.
² Division of Infectious Disease and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
³ Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁴ CIBMTR© (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI, USA.
⁵ Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI, USA.
⁶ Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
⁷ Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
⁸ University of Miami, Miami, FL, USA.
⁹ Division of Pediatric Oncology/Hematology, Department of Pediatrics, Penn State Hershey Children's Hospital and College of Medicine, Hershey, PA, USA.
¹⁰ Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical Center, Worcester, MA, USA.
¹¹ Medical College of Wisconsin, Milwaukee, WI, USA.
¹² Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL, USA.
¹³ Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁴ Tom Baker Cancer Center, Calgary, AL, Canada.
¹⁵ Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
¹⁶ Division of Pediatric Allergy, Immunology & Bone Marrow Transplantation, Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA.
¹⁷ Texas Transplant Institute, San Antonio, TX, USA.
¹⁸ Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁹ Seidman Cancer Center, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA.
²⁰ Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden.
²¹ Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
²² Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, NC, USA.
²³ Houston Methodist Hospital, Houston, TX, USA.
²⁴ Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
²⁵ Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
²⁶ Division of Hematology, Oncology and Cellular Therapy, Rush University, Chicago, IL, USA.
²⁷ Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
²⁸ Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, WA, USA.
²⁹ Blood and Marrow Transplant Program and Host Defense Program, Divisions of Hematology/Oncology/Bone Marrow Transplant and Infectious Diseases, Nationwide Children's Hospital, Columbus, OH, USA.
³⁰ Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
³¹ Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
³² Division of Hematology/Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

PMID: 30546070
PMCID: PMC6565512
DOI: 10.1038/s41409-018-0401-4

Bacterial blood stream infections (BSIs), particularly post-engraftment BSIs, are associated with increased mortality after allogeneic hematopoietic cell transplantation

Celalettin Ustun et al. Bone Marrow Transplant. 2019 Aug.

. 2019 Aug;54(8):1254-1265.

doi: 10.1038/s41409-018-0401-4. Epub 2018 Dec 13.

Authors

Affiliations

¹ Division of Hematology, Oncology and Cellular Therapy, Rush University, Chicago, IL, USA. Celalettin_Ustun@rush.edu.
² Division of Infectious Disease and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
³ Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁴ CIBMTR© (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI, USA.
⁵ Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI, USA.
⁶ Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
⁷ Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
⁸ University of Miami, Miami, FL, USA.
⁹ Division of Pediatric Oncology/Hematology, Department of Pediatrics, Penn State Hershey Children's Hospital and College of Medicine, Hershey, PA, USA.
¹⁰ Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical Center, Worcester, MA, USA.
¹¹ Medical College of Wisconsin, Milwaukee, WI, USA.
¹² Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL, USA.
¹³ Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁴ Tom Baker Cancer Center, Calgary, AL, Canada.
¹⁵ Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
¹⁶ Division of Pediatric Allergy, Immunology & Bone Marrow Transplantation, Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA.
¹⁷ Texas Transplant Institute, San Antonio, TX, USA.
¹⁸ Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁹ Seidman Cancer Center, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA.
²⁰ Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden.
²¹ Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
²² Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, NC, USA.
²³ Houston Methodist Hospital, Houston, TX, USA.
²⁴ Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
²⁵ Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
²⁶ Division of Hematology, Oncology and Cellular Therapy, Rush University, Chicago, IL, USA.
²⁷ Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
²⁸ Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, WA, USA.
²⁹ Blood and Marrow Transplant Program and Host Defense Program, Divisions of Hematology/Oncology/Bone Marrow Transplant and Infectious Diseases, Nationwide Children's Hospital, Columbus, OH, USA.
³⁰ Pediatric Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
³¹ Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
³² Division of Hematology/Oncology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

PMID: 30546070
PMCID: PMC6565512
DOI: 10.1038/s41409-018-0401-4

Abstract

We analyzed CIBMTR data to evaluate the incidence of non-relapse mortality (NRM) and association with overall survival (OS) for bacterial blood stream infections (BSIs) occurring within 100 days of alloHCT in 2 different phases: pre-/peri-engraftment (BSI very early phase, BSI-VEP) and BSI post-engraftment (BSI occurring between 2 weeks after engraftment and day 100, late early phase, BSI-LEP). Of the 7128 alloHCT patients, 2656 (37%) had ≥1 BSI by day 100. BSI-VEP, BSI-LEP, and BSI-Both constituted 56% (n = 1492), 31% (n = 824), and 13% (n = 340) of total BSI, respectively. Starting in 2009, we observed a gradual decline in BSI incidence through 2012 (61-48%). Patients with BSI-VEP were more likely to receive a myeloablative conditioning (MAC) regimen with total body irradiation (TBI). NRM was significantly higher in patients with any BSI (RR 1.82 95% CI 1.63-2.04 for BSI-VEP, RR 2.46, 95% CI 2.05-2.96 for BSI-LEP, and RR 2.29, 95% CI 1.87-2.81 for BSI-Both) compared with those without BSI. OS was significantly lower in patients with any BSI compared with patients without BSI (RR 1.36, 95% CI 1.26-1.47 for BSI-VEP; RR 1.83, 95% CI 1.58-2.12 for BSI-LEP: RR 1.66, 95% CI 1.43-1.94 for BSI-Both). BSIs within day 100 after alloHCT are common and remain a risk factor for mortality.

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Conflict of interest statement

Conflict of Interest: The authors have no conflicts of interest to disclose.

Figures

**Figure 1**
A.Patients with BSI per documented bacteria involved in BSI-VEP (left column) and BSI-LEP (middle column) and BSI-Both (right column) within 100 days (presented as %). Most of the BSI in VEP and LEP are composed of CoNS, Enterobacteriaceae, and other GPC. B.Patients with BSI divided by episodes and single organism or polymicrobial infections. 63% of patients had no BSI whereas 9% of patients had ≥ 2 BSI.

**Figure 2.**
NRM curve for VEP-BSI vs. LEP-BSI vs Both VEP- and LEP-BSI vs. No BSI), starting day 100 after transplant. Patients with no BSI had a lower NRM.

**Figure 3.**
OS curve for VEP-BSI vs. LEP-BSI vs Both VEP- and LEP-BSI vs. No BSI), starting day 100 after transplant. Patients with LEP-BSI and Both-BSI especially had worse OS.

See this image and copyright information in PMC

References

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Bacterial blood stream infections (BSIs), particularly post-engraftment BSIs, are associated with increased mortality after allogeneic hematopoietic cell transplantation

Affiliations

Bacterial blood stream infections (BSIs), particularly post-engraftment BSIs, are associated with increased mortality after allogeneic hematopoietic cell transplantation

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous