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The incidence and impact of clostridioides difficile infection on transplant outcomes in acute leukemia and MDS after allogeneic hematopoietic cell transplant—a CIBMTR study

Bone Marrow Transplantation volume 58, pages 360–366 (2023)Cite this article

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Abstract

Clostridioides difficile infection (CDI) is common after allogeneic hematopoietic cell transplantation (alloHCT). The determination of incidence, risk factors, and impact of CDI on alloHCT outcomes is an unmet need. The study examines all patients aged 2 years and older who received first alloHCT for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or myelodysplastic syndrome (MDS) between 2013 and 2018 at US centers and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) data registry. In total, 826 patients with CDI and 6723 controls from 127 centers were analyzed. The cumulative incidence of CDI by day 100 was 18.7% (99% CI: 15–22.7%) and 10.2% (99% CI: 9.2–11.1%) in pediatric and adult patients, respectively, with a median time to diagnosis at day +13. CDI was associated with inferior overall survival (OS) (p = 0.0018) and a 2.58-fold [99% CI: 1.43–4.66; p < 0.001] increase in infection-related mortality (IRM). There was a significant overlap in the onset of acute graft versus host disease (aGVHD) and CDI. IRM increased to >4 fold when CDI + aGVHD was considered. Despite advances in the management of CDI, increased IRM and decreased OS still results from CDI.

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Fig. 1
Fig. 2: Overlap of CDI with Acute GVHD and Lower GI GVHD.

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Data availability

CIBMTR supports accessibility of research in accord with the National Institutes of Health (NIH) Data Sharing Policy and the National Cancer Institute (NCI) Cancer Moonshot Public Access and Data Sharing Policy. The CIBMTR only releases de-identified datasets that comply with all relevant global regulations regarding privacy and confidentiality.

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Acknowledgements

The CIBMTR is supported primarily by 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); HHSH250201700006C from the Health Resources and Services Administration (HRSA); and N00014–20–1–2832 and N00014–21–1–2954 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, and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptimmune; Adaptive Biotechnologies Corporation; ADC Therapeutics; Adienne SA; Allogene; Allovir, Inc.; Amgen, Inc.; Angiocrine; Anthem; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics; BeiGene; bluebird bio, inc.; Bristol Myers Squibb Co.; CareDx Inc.; CRISPR; CSL Behring; CytoSen Therapeutics, Inc.; Eurofins Viracor, DBA Eurofins Transplant Diagnostics; Gamida-Cell, Ltd.; Gilead; GlaxoSmithKline; HistoGenetics; Incyte Corporation; Iovance; Janssen Research & Development, LLC; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Kadmon, a Sanofi Company; Karius; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt Pharmaceuticals; Medac GmbH; Medexus Pharma; Merck & Co.; Mesoblast; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; OptumHealth; Orca Biosystems, Inc.; Ossium Health, Inc.; Pfizer, Inc.; Pharmacyclics, LLC, An AbbVie Company; Pluristem; PPD Development, LP; Sanofi; Sobi, Inc.; Stemcyte; Takeda Pharmaceuticals; Talaris Therapeutics; Terumo Blood and Cell Technologies; TG Therapeutics; Vertex Pharmaceuticals; Vor Biopharma Inc.; Xenikos BV.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Medicine, UMass Memorial Medical Center, Worcester, MA, USA

    Muthalagu Ramanathan

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

    Soyoung Kim

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

    Soyoung Kim, Naya He, Min Chen & Marcie Riches

  4. Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Medicine, University of Wisconsin, Madison, WI, USA

    Peiman Hematti

  5. Divisions of Hematology/Oncology & Infectious Diseases, BMT & Cellular Therapy Program, Medical College of Wisconsin, Milwaukee, WI, USA

    Muhammad Bilal Abid

  6. Department of Pediatric Hematology, Oncology, and Blood and Marrow Transplantation, Cleveland Clinic Children’s Hospital, Cleveland, OH, USA

    Seth J. Rotz

  7. Children’s Healthcare of Atlanta, Emory University, Atlanta, GA, USA

    Kirsten M. Williams

  8. University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA

    Hillard M. Lazarus

  9. Bone Marrow Transplant Program, Penn State Cancer Institute, Hershey, PA, USA

    Baldeep Wirk

  10. Divisions of Infectious Diseases and Clinical Pharmacology, Department of Pediatrics, Children’s Mercy Kansas City and University of Missouri at Kansas City, Kansas City, MO, USA

    Dwight E. Yin

  11. Experimental Transplantation and Immunotherapy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Christopher G. Kanakry

  12. Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Miguel-Angel Perales

  13. Department of Medicine, Weill Cornell Medicine, New York, NY, USA

    Miguel-Angel Perales

  14. M.D. Anderson Cancer Center, Houston, TX, USA

    Roy F. Chemaly

  15. Cincinnati Children’s Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, OH, USA

    Christopher E. Dandoy

  16. Division of Hematology/Oncology/Cell Therapy, Rush University, Chicago, IL, USA

    Celalettin Ustun

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Contributions

MRamanathan and CU were responsible for designing the observational study, writing the paper, interpreting results, and updating references. SK, NH, and MC were responsible for extracting and analyzing data and creating figures and tables. PH, MBA, SJR, KMW, HML, BW, and DEY provided feedback for the paper. CGK, MAP, RFC, CD, and MRiches contributed to study design, writing the paper, interpreting results and updating references.

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Correspondence to Muthalagu Ramanathan.

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Competing interests

Dr KMW reports having a R01 with NHLBI on biomarkers of engraftment; a TRP grant with Leukemia Lymphoma Society to develop a novel immunotherapy for AML; and having received payments from Rising Tide, NIH, and LLS for grant reviews. Dr MAP reports honoraria from Abbvie, Astellas, Bristol-Myers Squibb, Celgene, Equilium, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Novartis, Nektar Therapeutics, Omeros, OrcaBio, Takeda, and VectivBio AG, Vor Biopharma; serves on DSMBs for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier, and the scientific advisory board of NexImmune; has ownership interests in NexImmune and Omerosl; has received research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, and Novartis; received payments from Adboards/Consulting for Novartis, Merck, Omeros, Incyte. Relationships: VP, ASTCT. Dr RFC reports as a consultant and/or Advisor for Ansun BioPharma, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Oxford Immunotec USA, Inc., Pulmotect, Inc., Takeda, Genentech, Karius, ADMA Biologics, Molecular Partners, and Xenex Laboratories; having received grant/research support from Ansun BioPharma, Eurofins-Viracor, Inc., Merck & Co., Inc., Takeda; Karius, Inc., Oxford Immunotec USA, Inc., and Genentech. Dr CED has received honorarium from Omeros and Alexion Pharmaceuticals. Dr MRiches reports IQVIA Biotech, employee (as of 1/10/22); Jazz Pharmaceuticals (research funding to university- end 1/10/22); Atara Bio-Pharma (research funding to university- end 1/10/22).

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Ramanathan, M., Kim, S., He, N. et al. The incidence and impact of clostridioides difficile infection on transplant outcomes in acute leukemia and MDS after allogeneic hematopoietic cell transplant—a CIBMTR study. Bone Marrow Transplant 58, 360–366 (2023). https://doi.org/10.1038/s41409-022-01896-z

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