Impact of early CMV reactivation in cord blood stem cell recipients in the current era

• Type of Material: Article
• Authors: Muthalagu Ramanathan, UMass Memorial Medical Center; Pierre Teira, University of Montreal; Minoo Battiwalla, National Heart, Lung, and Blood Institute; John Barrett, National Heart, Lung, and Blood Institute; Kwang Woo Ahn, Medical College of Wisconsin; Min Chen, Medical College of Wisconsin; Jamie Green, University of Minnesota; Mary Laughlin, Cleveland Cord Blood Center; Hillard M. Lazarus, University Hospitals Case Medical Center; David Marks, University Hospitals Bristol NHS Trust; Ayman Saad, University of Alabama at Birmingham; Matthew Seftel, Princess Margaret Cancer Centre; Wael Saber, National Heart, Lung, and Blood Institute; Bipin Savani, Vanderbilt University; Edmund Waller, Emory University; John Wingard, University of Florida; Jeffery J. Auletta, Nationwide Children’s Hospital; Caroline A. Lindemans, University Medical Center Utrecht; Michael Boeckh, Fred Hutchinson Cancer Research Center; Marcie L. Riches, University of North Carolina at Chapel Hill
• Language: English
• Date: 2016-08
• Publisher: Nature Publishing Group: Open Access Hybrid Model Option B
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Macmillan Publishers Limited, part of Springer Nature.
• Final Published Version (URL): http://dx.doi.org/10.1038/bmt.2016.89
• Title of Journal or Parent Work: Bone Marrow Transplantation
• ISSN: 0268-3369
• Volume: 51
• Issue: 8
• Start Page: 1113
• End Page: 1120
• 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. Corporate Members have been denoted by the ‘*’ symbol.
• Keywords: Transplantation; Hematology; TRANSPLANT RECIPIENTS; SEROSTATUS; T-CELLS; CYTOMEGALOVIRUS REACTIVATION; Allogeneic transplant; Science & Technology; DISEASE; DONOR; ALLO-SCT; Leukemia; Oncology; Immunology; Life Sciences & Biomedicine; Cytomegalovirus; ACUTE MYELOID-LEUKEMIA; BONE-MARROW; Umbilical cord blood; RELAPSE RISK EVIDENCE; Biophysics
• Research Categories: Biology, Virology; Health Sciences, Oncology

Abstract

Several studies have reported an association between CMV reactivation and a decreased incidence of relapse for AML after adult donor allogeneic hematopoietic cell transplantation (HCT). Limited data, however, are available on the impact of CMV reactivation on relapse after cord blood (CB) stem cell transplantation. The unique combination of higher incidence of CMV reactivation in the seropositive recipient and lower incidence of graft versus host disease (GvHD) in CB HCT permits a valuable design to analyze the impact of CMV reactivation. Data from 1684 patients transplanted with CB between 2003 and 2010 for AML and ALL were analyzed. The median time to CMV reactivation was 34 days (range: 2-287). CMV reactivation and positive CMV serology were associated with increased non-relapse mortality (NRM) among both AML and ALL CB recipients (reactivation, AML: relative risk (RR) 1.41 (1.07-1.85); ALL: 1.60 (1.14-2.23); Serology, AML: RR 1.39 (1.05-1.85), ALL: RR 1.61 (1.18-2.19)). For patients with ALL, but not those with AML, this yielded inferior overall survival (P < 0.005). Risk of relapse was not influenced by CMV reactivation or positive CMV serostatus for either disease.