title: Infections after Transplantation of Bone Marrow or Peripheral Blood Stem Cells from Unrelated Donors.
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.
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota. Electronic address: vanbu004@umn.edu.
authors.forename: Jo-Anne H
authors.initials: JH
authors.lastname: Young
authors.affiliation: BRL: Institute for Health and Society, Division of Biostatistics; MMH: Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Brent R
authors.initials: BR
authors.lastname: Logan
authors.affiliation: Blood and Bone Marrow Transplant Clinical Trials Network, The EMMES Corporation, Rockville, Maryland.
authors.forename: Juan
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Medicine, Shands Cancer Center, University of Florida, Gainesville, Florida.
authors.forename: John R
authors.initials: JR
authors.lastname: Wingard
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.affiliation: Blood and Bone Marrow Transplant Clinical Trials Network, The EMMES Corporation, Rockville, Maryland.
authors.forename: Cathryn
authors.initials: C
authors.lastname: Mudrick
authors.affiliation: Blood and Bone Marrow Transplant Clinical Trials Network, The EMMES Corporation, Rockville, Maryland.
authors.forename: Kristin
authors.initials: K
authors.lastname: Knust
authors.affiliation: BRL: Institute for Health and Society, Division of Biostatistics; MMH: Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Horowitz
authors.affiliation: National Marrow Donor Program, Minneapolis, Minnesota.
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Confer
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Erik R
authors.initials: ER
authors.lastname: Dubberke
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Pergam
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Marty
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Oregon Health & Science University, Portland, Oregon.
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Strasfeld
authors.affiliation: Department of Medicine, Stanford University, Palo Alto, California.
authors.forename: Janice Wes M
authors.initials: JWM
authors.lastname: Brown
authors.affiliation: Department of Medicine, Emory University, Atlanta, Georgia.
authors.forename: Amelia A
authors.initials: AA
authors.lastname: Langston
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Mindy G
authors.initials: MG
authors.lastname: Schuster
authors.affiliation: Department of Internal Medicine, Division of Infectious Disease, Univeristy of Michigan, Ann Arbor, Michigan.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kaul
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Ohio State University, Columbus, Ohio.
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Martin
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000379:methods*; D005260:Female; D006801:Humans; D007239:Infections / Q000209:etiology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D061349:Unrelated Donors
keywords: Aspergillosis; Bacteremia; Cytomegalovirus; Infection; Pre-engraftment; Unrelated donor transplantation