The Incidence and Impact of Clostridioides Difficile Infection on Transplant Outcomes in Acute Leukemia and MDS after Allogeneic Hematopoietic Cell Transplant– A CIBMTR Study

• Type of Material: Article
• Authors: Muthalagu Ramanathan, University of Massachussets, Worcester, MA; Soyoung Kim, Medical College of Wisconsin; Naya He, Medical College of Wisconsin; Min Chen, Medical College of Wisconsin; Peiman Hematti, University of Wisconsin, Madison, Wisconsin; Muhammad Bilal Abid, Medical College of Wisconsin; Seth J Rotz, Cleveland Clinic Children’s Hospital; Kirsten Marie Williams, Emory University; Hillard M. Lazarus, Case Western Reserve University; Baldeep Wirk, Penn State Cancer Institute; Dwight E Yin, University of Missouri at Kansas City, Kansas City, Missouri; Christopher G Kanakry, National Institutes of Health; Miguel-Angel Perales, Memorial Sloan Kettering Cancer Center; Roy F Chemaly, M.D. Anderson Cancer Center; Christopher Dandoy, University of Cincinnati School of Medicine, Cincinnati, Ohio; Marcie Riches, Medical College of Wisconsin; Celalettin Ustun, Rush University
• Language: English
• Date: 2022-12-21
• Publisher: Springer Nature
• Publication Version: Final Published Version
• Copyright Statement: © 2022, The Author(s), under exclusive licence to Springer Nature Limited
• Final Published Version (URL): https://doi.org/10.1038%2Fs41409-022-01896-z
• Title of Journal or Parent Work: Bone Marrow Transplantation
• Volume: 58
• Start Page: 360
• End Page: 366
• Grant/Funding Information: 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.
• Keywords: Transplant Outcomes; Clostridioides Difficile Infection; CIBMTR; Acute Leukemia and MDS; Allogeneic Hematopoietic Cell Transplant
• Research Categories: Health Sciences, Oncology; Health Sciences, Medicine and Surgery

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 two 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.