title: Poor immune reconstitution is associated with symptomatic BK polyomavirus viruria in allogeneic stem cell transplant recipients.
abstract: BACKGROUND
  BK polyomavirus (BKPyV) infections are known indicators of immune suppression in hematopoietic stem cell transplant (HSCT) recipients; they can lead to hemorrhagic cystitis, ureteral stenosis, renal dysfunction, and prolonged hospital stays. In this study, we determined transplant-associated variables and immune parameters that can predict for the risk of BKPyV viruria. We hypothesized that BKPyV infection is a marker of poor immune recovery.
  
  
  METHODS
  We analyzed all engrafted patients undergoing first allogeneic HSCT at MD Anderson Cancer Center in Houston between January 2004 and December 2012. We evaluated their immune parameters and their transplant-associated factors. BKPyV positivity was defined as BKPyV detection in urine by polymerase chain reaction testing. Cox proportional hazards model, as well as competing risk analysis method using subdistribution hazard models with death as competing risk, were applied to assess risk of BKPyV viruria.
  
  
  RESULTS
  We identified a total of 2477 patients with a median age of 52 years. BKPyV viruria was manifest in 25% (n=629) of the patients. The median time from transplantation to BKPyV viruria development was 42 days among the patients who had BKPyV viruria. On multivariate analysis, tumor type, acute GVHD, chronic GVHD, myeloablative conditioning regimen, cord blood as the graft source, CD3+, CD4+, CD8+, CD56+, NK counts, and low platelet count were shown to be significantly associated with BKPyV infection. These finding were further confirmed when models incorporating the competing risk of death yielded similar findings.
  
  
  CONCLUSIONS
  In this study, we report significant associations between BKPyV reactivation following allogeneic HSCT and suppressed immune variables. In addition, this study provides valuable information on the immune status of HSCT recipients as a predictor of BKPyV infections that may in turn help us formulate plans for more effective prevention and treatment of this infection.
authors.affiliation: Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ala
authors.initials: A
authors.lastname: Abudayyeh
authors.affiliation: Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Hamdi
authors.affiliation: Division of Medical Oncology, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Maen
authors.initials: M
authors.lastname: Abdelrahim
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Emergency Medicine and Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Valda D
authors.initials: VD
authors.lastname: Page
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Rondon
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Borje S
authors.initials: BS
authors.lastname: Andersson
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Aimaz
authors.initials: A
authors.lastname: Afrough
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Martinez
authors.affiliation: Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Tarrand
authors.affiliation: Department of Infectious Diseases, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: David
authors.initials: D
authors.lastname: Marin
authors.affiliation: Department of Transplant Surgery, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: A Osama
authors.initials: AO
authors.lastname: Gaber
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Betul
authors.initials: B
authors.lastname: Oran
authors.affiliation: Department of Infectious Diseases, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Roy F
authors.initials: RF
authors.lastname: Chemaly
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sairah
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Division of Cardiology, Interventional Cardiology, Loma Linda University Health, Loma Linda, CA, USA.
authors.forename: Islam
authors.initials: I
authors.lastname: Abudayyeh
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Olson
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Jones
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Uday
authors.initials: U
authors.lastname: Popat
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Katayoun
authors.initials: K
authors.lastname: Rezvani
mesh_terms: D001739:BK Virus / Q000302:isolation & purification / Q000502:physiology*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000009:adverse effects / Q000627:therapeutic use; D027601:Polyomavirus Infections / Q000276:immunology* / Q000652:urine / Q000821:virology; D012189:Retrospective Studies; D018570:Risk Assessment; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014184:Transplantation, Homologous / Q000009:adverse effects; D014412:Tumor Virus Infections / Q000276:immunology* / Q000652:urine / Q000821:virology; D014570:Urologic Diseases / Q000276:immunology* / Q000652:urine / Q000821:virology; D014775:Virus Activation / Q000276:immunology*
chemical_list: D019653:Myeloablative Agonists
keywords: BK virus; T-cell suppression; allogeneic stem cell transplant; immune suppression