Infection Rates among Acute Leukemia Patients Receiving Alternative Donor Hematopoietic Cell Transplantation

• Type of Material: Article
• Authors: Karen Ballen, Massachusetts General Hospital; Kwang Woo Ahn, Medical College of Wisconsin; Min Chen, Medical College of Wisconsin; Hisham Abdel-Azim, University of Southern California; Ibrahim Ahmed, The Children’s Mercy Hospitals and Clinics; Mahmoud Aljurf, King Faisal Specialist Hospital Center & Research; Joseph Antin, Dana-Farber Cancer Institute; Ami S. Bhatt, Stanford University; Michael Boeckh, Fred Hutchinson Cancer Research Center; George Chen, Roswell Park Cancer Institute; Christopher Dandoy, Cincinnati Children’s Hospital Medical Center; Biju George, Christian Medical College; Mary J. Laughlin, Cleveland Cord Blood Center; Hillard M. Lazarus, University Hospitals Case Medical Center; Margaret L. MacMillan, University of Minnesota; David A. Margolis, Medical College of Wisconsin; David I. Marks, University Hospitals Bristol NHS Trust; Maxim Norkin, University of Florida; Joseph Rosenthal, City of Hope National Medical Center; Ayman Saad, University of Alabama Birmingham; Bipin Savani, Vanderbilt University; Harry C. Schouten, Academische Ziekenhuis; Jan Storek, University of Calgary; Paul Szabolcs, Children's National Health System; Celalettin Ustun, University of Minnesota; Michael R. Verneris, University of Minnesota; Edmund Waller, Emory University; Daniel J. Weisdorf, University of Minnesota; Kirsten M. Williams, National Cancer Institute; John R. Wingard, University of Florida; Baldeep Wirk, Seattle Cancer Care Alliance; Tom Wolfs, Wilhelmina Children's Hospital; Jo-Anne H. Young, University of Minnesota; Jeffrey Auletta, Nationwide Children's Hospital; Krishna V. Komanduri, University of Miami; Caroline Lindemans, University Medical Center Utrecht; Marcie L. Riches, University of North Carolina Chapel Hill
• Language: English
• Date: 2016-06-22
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 The American Society for Blood and Marrow Transplantation
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbmt.2016.06.012
• Title of Journal or Parent Work: Biology of Blood and Marrow Transplantation
• ISSN: 1083-8791
• Volume: 22
• Issue: 9
• Start Page: 1636
• End Page: 1645
• Grant/Funding Information: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement 5U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from Alexion; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Be the Match Foundation; *Bristol Myers Squibb Oncology; *Celgene Corporation; *Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Genentech, Inc.; Genzyme Corporation; *Gilead Sciences, Inc.; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; *Jazz Pharmaceuticals, Inc.; Jeff Gordon Children’s Foundation; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc.; Mesoblast; *Millennium: The Takeda Oncology Co.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Neovii Biotech NA, Inc.; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Otsuka Pharmaceutical Co, Ltd. – Japan; Oxford Immunotec; Perkin Elmer, Inc.; Pharmacyclics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; *Spectrum Pharmaceuticals, Inc.; St. Baldrick’s Foundation; *Sunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Telomere Diagnostics, Inc.; TerumoBCT; Therakos, Inc.; University of Minnesota; and *Wellpoint, Inc.
• Keywords: Science & Technology; UNRELATED DONORS; INVASIVE FUNGAL DISEASE; HEMATOLOGIC MALIGNANCIES; Transplantation; CONDITIONING REGIMEN; Leukemia; Life Sciences & Biomedicine; ACUTE MYELOID-LEUKEMIA; UMBILICAL-CORD BLOOD; IMMUNE RECONSTITUTION; Infection; Umbilical cord blood; BONE-MARROW; Immunology; PERIPHERAL-BLOOD; Hematology; INTERNATIONAL BLOOD
• Research Categories: Health Sciences, Oncology

Abstract

Alternative graft sources (umbilical cord blood [UCB], matched unrelated donors [MUD] , or mismatched unrelated donors [MMUD]) enable patients without a matched sibling donor to receive potentially curative hematopoietic cell transplantation (HCT). Retrospective studies demonstrate comparable outcomes among different graft sources. However, the risk and types of infections have not been compared among graft sources. Such information may influence the choice of a particular graft source. We compared the incidence of bacterial, viral, and fungal infections in 1781 adults with acute leukemia who received alternative donor HCT (UCB, n= 568; MUD, n = 930; MMUD, n = 283) between 2008 and 2011. The incidences of bacterial infection at 1 year were 72%, 59%, and 65% (P  <  .0001) for UCB, MUD, and MMUD, respectively. Incidences of viral infection at 1 year were 68%, 45%, and 53% (P  <  .0001) for UCB, MUD, and MMUD, respectively. In multivariable analysis, bacterial, fungal, and viral infections were more common after either UCB or MMUD than after MUD (P  <  .0001). Bacterial and viral but not fungal infections were more common after UCB than MMUD (P = .0009 and < .0001, respectively). The presence of viral infection was not associated with an increased mortality. Overall survival (OS) was comparable among UCB and MMUD patients with Karnofsky performance status (KPS) ≥ 90% but was inferior for UCB for patients with KPS  <  90%. Bacterial and fungal infections were associated with poorer OS. Future strategies focusing on infection prevention and treatment are indicated to improve HCT outcomes.