Infections after Transplantation of Bone Marrow or Peripheral Blood Stem Cells from Unrelated Donors

Jo Anne H Young, Brent R. Logan, Juan Wu, John R. Wingard, Daniel J. Weisdorf, Cathryn Mudrick, Kristin Knust, Mary M. Horowitz, Dennis L. Confer, Erik R. Dubberke, Steven A. Pergam, Francisco M. Marty, Lynne M. Strasfeld, Janice M. Brown, Amelia A. Langston, Mindy G. Schuster, Daniel R. Kaul, Stanley I. Martin, Claudio Anasetti

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61 Scopus citations

Abstract

Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft-versus-host disease are the 2 major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (Blood and Marrow Transplant Clinical Trials Network [BMT CTN] 0201) of transplantation of bone marrow (BM) versus peripheral blood stem cells (PBSC) from unrelated donors showed no significant differences in 2-year survival between these graft sources. In an effort to provide data regarding whether BM or PBSC could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2 years after transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201 of 249 (81%) of the evaluable patients had received a BM graft and 183 of 250 (73%) had received a PBSC graft. Of 1347 infection episodes, 373 were severe and 123 were life-threatening and/or fatal; 710 (53%) of these episodes occurred on the BM arm and 637 (47%) on the PBSC arm, resulting in a 2-year cumulative incidence 84.7% (95% confidence interval [CI], 79.6 to 89.8) for BM versus 79.7% (95% CI, 73.9 to 85.5) for PBSC, P =013. The majority of these episodes, 810 (60%), were due to bacteria, with a 2-year cumulative incidence of 72.1% and 62.9% in BM versus PBSC recipients, respectively (P =003). The cumulative incidence of bloodstream bacterial infections during the first 100 days was 44.8% (95% CI, 38.5 to 51.1) for BM versus 35.0% (95% CI, 28.9 to 41.1) for PBSC (P =027). The total infection density (number of infection events/100 patient days at risk) was.67 for BM and.60 for PBSC. The overall infection density for bacterial infections was.4 in both arms; for viral infections, it was.2 in both arms; and for fungal/parasitic infections, it was.04 and.05 for BM and PBSC, respectively. The cumulative incidence of infection before engraftment was 47.9% (95% CI, 41.5 to 53.9) for BM versus 32.8% (95% CI, 27.1 to 38.7) for PBSC (P =002), possibly related to quicker neutrophil engraftment using PBSC. Infections remain frequent after unrelated donor hematopoietic cell transplantation, particularly after BM grafts.

Original languageEnglish (US)
Pages (from-to)359-370
Number of pages12
JournalBiology of Blood and Marrow Transplantation
Volume22
Issue number2
DOIs
StatePublished - Feb 1 2016

Bibliographical note

Funding Information:
This study was supported by a grant from the National Heart, Lung, and Blood Institute and the National Cancer Institute (U10HL069294), by the Office of Naval Research, and by the National Marrow Donor Program. Disclosure forms were provided by the authors. The authors thank the transplantation center teams in the United States and Canada for enrolling patients in this trial; the donor-center teams in the United States, Canada, and Germany for recruiting the donors for the trial; and the National Marrow Donor Program coordinating center for facilitating the transplantations. The authors thank the infectious disease auditors at each center: Nathalie Lachapelle and Jean Roy (Hôpital Maisonneuve-Rosemont), Susan Durham (Cohen Children''s Medical Center), Karen Parrott (University of Iowa Hospitals and Clinics), Andrea Ortega (Hackensack University Medical Center), Mindy Shuster (University of Pennsylvania Cancer Center), Jessica Piggee (Vanderbilt University Medical Center), Margaret Shea and Francisco Marty (Dana-Farber Cancer Institute and Brigham and Women''s Hospital), Erik Dubberke (Washington University: Barnes-Jewish), Juliana Ongley (University of California, San Diego), Lisa Malick (University of Maryland Cancer Center), Stanley Martin (Ohio State: Arthur G. James Cancer Hospital), Valerie Dorcas (Queen Elizabeth II Health Sciences Centre), JoDell McCracken (Texas Transplant Institute), Lisa Dutton (Mayo Clinic, Rochester), Lynne Strasfeld (Oregon Health & Science University), Daniel Kaul (University of Michigan Health System), Ginger Butterworth (Baylor University Medical Center), Lisa Williams (University of Alabama at Birmingham), Michael Pulsipher (Primary Children''s Hospital/Utah BMT), David Hurd (Wake Forest University), Tia Thomas (Washington University: St. Louis Children''s Hospital), Melissa Moynihan (Vancouver General Hospital), Amy O''Sullivan, Brittni Prosdocimo, and Mounzer Agha (University of Pittsburgh Cancer Institute), Janice (Wes) Brown (Stanford Hospital and Clinics), Greg McFadden (University of Nebraska Medical Center), Lynn Savoie (Tom Baker Cancer Centre), Patti Cunningham (Oklahoma University Medical Center), Adina Londrc (City of Hope National Medical Center), John Wingard (University of Florida: College of Medicine), Rebecca Gerkin (Emory University Hospital), Tammy DeGelder (McMaster University Medical Centre: Hamilton Health Sciences), Shaun DeJarnette and Abhyankar (University of Kansas Medical Center), Carol Cutrone (Loyola University Medical Center), Sofia Qureshi (MD Anderson Cancer Center), Jueleah Expose''-Spencer (University of California, San Francisco), Isabel Belen (University of Toronto: Princess Margaret), Jessica Greene (Roswell Park Cancer Institute), Mitch Horwitz (Duke University Medical Center), and Steven Pergam (Fred Hutchinson Cancer Research Center). Financial disclosure: The authors declare no financial disclosures relevant to the work presented in this report. Conflict of interest statement: The authors declare no competing financial interests. Authorship statement: J.H.Y. and D.J.W. designed the infectious disease analysis for this study protocol and wrote the paper; C.A., J.R.W., M.M.H., and D.J.W. were senior advisors in the design, conduct, and analysis of the study; K.K. and C.M. organized and maintained the database, J.H.Y., J.R.W., E.R.D., S.A.P., F.M.M., L.M.S., J.M.B., A.A.L., M.G.S., D.R.K., and S.I.M. audited many infection summaries; J.W. and J.H.Y. analyzed data; B.R.L., and J.W. provided statistical analysis; all authors reviewed and provided insightful comments to better the manuscript; and J.W. and J.H.Y. drew the figures.

Keywords

  • Aspergillosis
  • Bacteremia
  • Cytomegalovirus
  • Infection
  • Pre-engraftment
  • Unrelated donor transplantation

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