title: Infectious Risk after Allogeneic Hematopoietic Cell Transplantation Complicated by Acute Graft-versus-Host Disease.
abstract: The occurrence of infections after allogeneic hematopoietic stem cell transplantation (HCT) is nearly universal. However, the relationship between infections and graft-versus-host disease (GVHD) is complex and attribution of infectious-related mortality is highly inconsistent, making comparison of infectious complication rates across allogeneic HCT clinical studies difficult. We categorized infectious complications from diagnosis or 1 year before HCT (whichever occurred later) through 2 years after HCT according to timing, frequency, causative organism, severity, and contribution to mortality for 431 consecutive patients who underwent allogeneic HCT from 2008 to 2011. We then assessed the contribution of risk factors, such as the frequency of pre-HCT infections and post-HCT GVHD, on post-HCT infection frequency and severity. We found that each pre-HCT bacterial infection/year leads to an additional 2.15 post-HCT bacterial infection/year (P = .004). Pre-HCT viral and fungal infections were not predictors for post-HCT infections. Acute GVHD (aGVHD) significantly increased the risk of developing life-threatening (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.33 to 2.90) and fatal (HR, 2.8; 95% CI, 1.10 to 7.08) infections. Furthermore, patients who develop aGVHD experienced ~60% more infections than patients who never develop aGVHD. Quantification of infection frequency and severity for patients with and without GVHD may facilitate comparison of infectious outcomes across allogeneic HCT trials.
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan; Pediatric Hematology/Oncology, Phoenix Children's Hospital, Phoenix, Arizona. Electronic address: hmiller2@phoenixchildrens.com.
authors.forename: Holly K
authors.initials: HK
authors.lastname: Miller
authors.affiliation: School of Public Health, University of Michigan, Ann Arbor, Michigan.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Braun
authors.affiliation: Division of Pediatric Infectious Disease, University of Michigan, Ann Arbor, Michigan.
authors.forename: Terri
authors.initials: T
authors.lastname: Stillwell
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Harris
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Sung
authors.initials: S
authors.lastname: Choi
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: James
authors.initials: J
authors.lastname: Connelly
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Daniel
authors.initials: D
authors.lastname: Couriel
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Steven
authors.initials: S
authors.lastname: Goldstein
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Kitko
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: John
authors.initials: J
authors.lastname: Magenau
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Attaphol
authors.initials: A
authors.lastname: Pawarode
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Pavan
authors.initials: P
authors.lastname: Reddy
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Mary
authors.initials: M
authors.lastname: Riwes
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Yanik
authors.affiliation: Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan; Division of Pediatric Infectious Disease, University of Michigan, Ann Arbor, Michigan; Blood and Marrow Transplant Program, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: John E
authors.initials: JE
authors.lastname: Levine
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000150:complications* / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D007239:Infections / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous; D055815:Young Adult
keywords: Acute graft-versus-host-disease; Fatal infection; Infection