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Incidence of bacterial blood stream infections in patients with acute GVHD

Bone Marrow Transplantation volume 60, pages 52–57 (2025)Cite this article

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Abstract

Bacterial bloodstream infections (BSI) can be a substantial contributor to complications of GVHD treatment. The aim of this study was to determine the risk for BSI from neutrophil engraftment through day 100 post transplant in patients with acute GVHD (AGVHD) based on organ involvement and severity. Patients (n = 4064) who underwent an allogeneic hematopoietic stem cell transplant (HCT) reported to the CIBMTR registry were analyzed. Grade II-IV AGVHD occurred in 1607 (39.5%) patients and was associated with a greater day-100 incidence of post engraftment BSI than with grade 0/I (24.9 vs. 15.3%). Patients with grade III/IV AGVHD had the highest BSI risk (HR 2.45; 95% CI 1.99–3.0; p < 0.0001). Lower GI involvement increased BSI risk (HR 1.54; 95% CI 1.17–2.02; p = 0.0019). BSI post-engraftment through day 100 was associated with worse survival (HR 1.64, 95% CI 1.43–1.87; p < 0.001) and higher non-relapse mortality (NRM), (HR 2.22; 95% CI 1.91–2.59; p < 0.001). Those with stage III/IV GI involvement are at highest risk for BSI. Future studies evaluating novel methods for preventing BSI in these high risk populations are needed to reduce mortality associated with AGVHD.

Highlights

  • Bacterial blood stream infections are more common in patients with Grade II-IV AGVHD with roughly 25% of these patients developing at least one BSI by day-100.

  • Patients with grade III/IV AGVHD and those with lower gastrointestinal involvement are at the highest risk for BSI.

  • Patients who experience a BSI by day 100 have worse survival and over a two-fold higher probability for non-relapse mortality.

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Data availability

The final analysis dataset will be posted to the CIBMTR website at: https://cibmtr.org/CIBMTR/Resources/Publicly-Available-Datasets#.

References

  1. Cusatis R, Litovich C, Feng Z, Allbee-Johnson M, Kapfhammer M, Mattila D, et al. Current trends and outcomes in cellular therapy activity in the United States, including prospective Patient Reported Outcomes data collection within the CIBMTR registry. Transplant Cell Ther. 2024;24:S2666–6367.

  2. Daly A, McAfee S, Dey B, Colby C, Schulte L, Yeap B, et al. Nonmyeloablative bone marrow transplantation: Infectious complications in 65 recipients of HLA-identical and mismatched transplants. Biol Blood Marrow Transpl. 2003;9:373–82.

    Article  Google Scholar 

  3. Cappellano P, Viscoli C, Bruzzi P, Van Lint MT, Pereira CAP, Bacigalupo A. Epidemiology and risk factors for bloodstream infections after allogeneic hematopoietic stem cell transplantion. N Microbiol. 2007;30:89–99.

    Google Scholar 

  4. Miller HK, Braun TM, Stillwell T, Harris AC, Choi S, Connelly J, et al. Infectious risk after allogeneic hematopoietic cell transplantation complicated by acute graft-versus-host disease. Biol Blood Marrow Transpl. 2017;23:522–8.

    Article  Google Scholar 

  5. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J. et al. Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective. Preface Bone Marrow Transpl. 2009;44:453–5.

    Article  CAS  Google Scholar 

  6. Mori Y, Yoshimoto G, Nishida R, Sugio T, Miyawaki K, Shima T, et al. Gastrointestinal graft-versus-host disease is a risk factor for postengraftment bloodstream infection in allogeneic hematopoietic stem cell transplant recipients. Biol Blood Marrow Transpl. 2018;24:2302–9.

    Article  Google Scholar 

  7. Inoue Y, Okinaka K, Fuji S, Inamoto Y, Uchida N, Toya T, et al. Severe acute graft-versus-host disease increases the incidence of blood stream infection and mortality after allogeneic hematopoietic cell transplantation: Japanese transplant registry study. Bone Marrow Transpl. 2021;56:2125–36.

    Article  Google Scholar 

  8. Modi A, Rybicki L, Majhail NS, Mossad SB. Severity of acute gastrointestinal graft-vs-host disease is associated with incidence of bloodstream infection after adult allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis. 2020;22:e13217.

    Article  PubMed  Google Scholar 

  9. Levinson A, Pinkney K, Jin Z, Bhatia M, Kung AL, Foca MD, et al. Acute gastrointestinal graft-vs-host disease is associated with increased enteric bacterial bloodstream infection density in pediatric allogeneic hematopoietic cell transplant recipients. Clin Infect Dis. 2015;61:350–7.

    Article  CAS  PubMed  Google Scholar 

  10. Sepkowitz KA. Antibiotic prophylaxis in patients receiving hematopoietic stem cell transplant. Bone Marrow Transpl. 2002;29:367–71.

    Article  CAS  Google Scholar 

  11. Averbuch D, Tridello G, Hoek J, Mikulska M, Akan H, Yanez San Segundo L, et al. Antimicrobial resistance in gram-negative rods causing bacteremia in hematopoietic stem cell transplant recipients: intercontinental prospective study of the infectious diseases working party of the European bone marrow transplantation group. Clin Infect Dis. 2017;65:1819–28.

    Article  CAS  PubMed  Google Scholar 

  12. Macesic N, Morrissey CO, Cheng AC, Spencer A, Peleg AY. Changing microbial epidemiology in hematopoietic stem cell transplant recipients: increasing resistance over a 9-year period. Transpl Infect Dis. 2014;16:887–96.

    Article  CAS  PubMed  Google Scholar 

  13. Hauck CG, Chong PP, Miller MB, Jamieson K, Fine JP, Foster MC, et al. Increasing rates of fluoroquinolone resistance in Escherichia coli isolated from the blood and urine of patients with hematologic malignancies and stem cell transplant recipients. Pathog Immun. 2016;1:234–42.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Jenq RR, Taur Y, Devlin SM, Ponce DM, Goldberg JD, Ahr KF, et al. Intestinal blautia is associated with reduced death from graft-versus-host disease. Biol Blood Marrow Transpl. 2015;21:1373–83.

    Article  Google Scholar 

  15. Weber D, Hiergeist A, Weber M, Dettmer K, Wolff D, Hahn J, et al. Detrimental effect of broad-spectrum antibiotics on intestinal microbiome diversity in patients after allogeneic stem cell transplantation: lack of commensal sparing antibiotics. Clin Infect Dis. 2019;68:1303–10.

    Article  CAS  PubMed  Google Scholar 

  16. Weber D, Jenq RR, Peled JU, Taur Y, Hiergeist A, Koestler J, et al. Microbiota disruption induced by early use of broad-spectrum antibiotics is an independent risk factor of outcome after allogeneic stem cell transplantation. Biol Blood Marrow Transpl. 2017;23:845–52.

    Article  CAS  Google Scholar 

  17. Lee S-E, Lim J-Y, Ryu D-B, Kim TW, Park SS, Jeon YW, et al. Alteration of the intestinal microbiota by broad-spectrum antibiotic use correlates with the occurrence of intestinal graft-versus-host disease. Biol Blood Marrow Transpl. 2019;25:1933–43.

    Article  Google Scholar 

  18. Taur Y, Xavier JB, Lipuma L, Ubeda C, Goldberg J, Gobourne A, et al. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2012;55:905–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transpl. 1995;15:825–8.

    CAS  Google Scholar 

  20. Button JE, Autran CA, Reens AL, Cosetta CM, Smriga S, Ericson M, et al. Dosing a synbiotic of human milk lligosaccharides and B. infantis leads to reversible engraftment in healthy adult microbiomes without antibiotics. Cell Host Microbe. 2022;30:712–25.

    Article  CAS  PubMed  Google Scholar 

  21. Šuligoj T, Vigsnaes LK, Abbeele PVD, Apostolou A, Karalis K, Savva GM, et al. Effects of human milk oilgosaccarides on the adult gut microbiota and barrier function. effects of human milk oligosaccharides on the adult gut microbiota and barrier function. Nutrients. 2020;12:2808.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The CIBMTR is supported primarily by the Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); 75R60222C00011 from the Health Resources and Services Administration (HRSA); N00014-23-1-2057 from the Office of Naval Research; Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, Gateway for Cancer Research, Pediatric Transplantation and Cellular Therapy Consortium and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; ADC Therapeutics; Adienne SA; Alexion; Allogene; AlloVir, Inc.; Amgen, Inc.; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics; BeiGene; BioLineRX; Blue Spark Technologies; bluebird bio, inc.; Blueprint Medicines; Bristol Myers Squibb Co.; CareDx Inc.; CSL Behring; CytoSen Therapeutics, Inc.; DKMS; Eurofins Viracor, DBA Eurofins Transplant Diagnostics; Gamida-Cell, Ltd.; Gift of Life Biologics; Gift of Life Marrow Registry; GlaxoSmithKline; HistoGenetics; Incyte Corporation; Iovance; Janssen Research & Development, LLC; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karius; Kashi Clinical Laboratories; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Labcorp; Legend Biotech; Mallinckrodt Pharmaceuticals; Med Learning Group; Merck & Co.; Mesoblast; Millennium, the Takeda Oncology Co.; Miller Pharmacal Group, Inc.; Miltenyi Biotec, Inc.; MorphoSys; MSA-EDITLife; Neovii Pharmaceuticals AG; Novartis Pharmaceuticals Corporation; Omeros Corporation; OptumHealth; Orca Biosystems, Inc.; OriGen BioMedical; Ossium Health, Inc.; Pfizer, Inc.; Pharmacyclics, LLC, An AbbVie Company; PPD Development, LP; REGiMMUNE; Registry Partners; Rigel Pharmaceuticals; Sanofi; Sarah Cannon; Seagen Inc.; Sobi, Inc.; Stemcell Technologies; Stemline Technologies; STEMSOFT; Takeda Pharmaceuticals; Talaris Therapeutics; Vertex Pharmaceuticals; Vor Biopharma Inc.; WellSky; Xenikos BV.

Author information

Author notes

  1. These authors contributed equally: Whitney Wallis, Alison M. Gulbis.

Authors and Affiliations

  1. The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Whitney Wallis, Alison M. Gulbis & Amin M. Alousi

  2. Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI, USA

    Tao Wang

  3. CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI, USA

    Tao Wang & Stephanie J. Lee

  4. Fred Hutchinson Cancer Center, Seattle, WA, USA

    Catherine J. Lee & Stephanie J. Lee

  5. Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Akshay Sharma

  6. Aflac Cancer and Blood Disorders Center, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA

    Kirsten M. Williams

  7. Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center, Tampa, FL, USA

    Taiga Nishihori & Joseph Pidala

  8. Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    Taiga Nishihori

  9. Blood and Cancer Centre, Starship Children’s Hospital, Auckland, New Zealand

    Tim Prestidge

  10. Yale Cancer Center and Yale School of Medicine, New Haven, CT, USA

    Lohith Gowda

  11. Tennessee Oncology, Nashville, TN, USA

    Michael Byrne

  12. Kansas City VA Medical Center, Kansas, MO, USA

    Maxwell M. Krem

  13. Blood and Marrow Transplant Program, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    Margaret L. MacMillan

  14. Division of Pediatric Hematology/Oncology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA

    Carrie L. Kitko

  15. CIBMTR® (Center for International Blood and Marrow Transplant Research), National Marrow Donor Program/Be The Match, Minneapolis, MN, USA

    Stephen R. Spellman

Authors
  1. Whitney Wallis
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  2. Alison M. Gulbis
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  3. Tao Wang
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  4. Catherine J. Lee
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  5. Akshay Sharma
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  9. Lohith Gowda
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  14. Joseph Pidala
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  15. Stephen R. Spellman
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  16. Stephanie J. Lee
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  17. Amin M. Alousi
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Contributions

Conceptions and study design (WW, AMG, TW, SRS, AMA), Statistical analysis (TW), Drafting the manuscript (WW, AMA), Interpreting results and revising the manuscript (all authors).

Corresponding author

Correspondence to Amin M. Alousi.

Ethics declarations

Competing interests

Dr. C Lee reports advisory board participation for Sanofi, Kite, Kadmon, BMS, and Incyte; research funding from Incyte; steering board committee participation for Incyte; speakers panel participation for Kite; and consulting for Fresenius Kabi, Sanofi, and Mallinckrodt. Dr. Sharma reports Grant funds from CRISPR Therapeutics; Consulting fees from Spotlight Therapeutics, Medexus Inc., Vertex Pharmaceuticals, Sangamo Therapeutics and Editas Medicine; and is the St. Jude Children’s Research Hospital site principal investigator of clinical trials for genome editing of sickle cell disease sponsored by Vertex Pharmaceuticals/CRISPR Therapeutics (NCT03745287), Novartis Pharmaceuticals (NCT04443907) and Beam Therapeutics (NCT05456880). The industry sponsors provide funding for the clinical trial, which includes salary support paid to Dr. Sharma’s institution. Dr. Sharma has no direct financial interest in these therapies. Dr. Nishihori reports significant payments (research support) to the institution for clinical trial (Novartis), research support (drug supply only) to the institution for clinical trial (Karyopharm) and advisory board participation for Medexus. Dr. Kitko reports compensation for ad board for Horizon Therapeutics and Incyte and compensation for participation in CME lectures about GVHD for Sanofi, Physicians Education Resource and i3Health. Dr. Pidala reports consulting and advisory board membership for Syndax, CTI Biopharma, Amgen, Regeneron, and Incyte; and clinical trial support for Novartis, Amgen, Takeda, Janssen, Johnson and Johnson, Pharmacyclics, Abbvie, CTI Biopharma, and BMS. Dr. S Lee reports compensation (research funding) from Amgen, AstraZeneca, Incyte, Kadmon, Pfizer, Syndax; steering committee participation for Incyte; drug supply for Janssen; consulting for Mallinckrodt, Equillium, Kadmon, Novartis and Sanofi; and National Marrow Donor Program Board of Directors (uncompensated). All other authors declare no competing interests.

Ethics approval and consent to participate

This study was approved the NMDP Institutional Review Board, registration number IRB00001253. All patients provided written informed consent for research participation and data submission, in accordance with the Declaration of Helsinki.

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Wallis, W., Gulbis, A.M., Wang, T. et al. Incidence of bacterial blood stream infections in patients with acute GVHD. Bone Marrow Transplant 60, 52–57 (2025). https://doi.org/10.1038/s41409-024-02426-9

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