title: BK viremia precedes hemorrhagic cystitis in children undergoing allogeneic hematopoietic stem cell transplantation.
abstract: BK virus is associated with hemorrhagic cystitis after hematopoietic stem cell transplantation (HSCT), although evidence supporting a causal relationship remains limited. Although BK viruria is common after HSCT, BK viremia may better predict clinically significant cystitis, similar to its predictive value for nephropathy after kidney transplantation. We hypothesized that BK viremia would precede hemorrhagic cystitis in a cohort of 88 consecutive children prospectively enrolled to originally study thrombotic microangiopathy in the first 100 days after allogeneic HSCT. Cox regression models with time-varying covariates assessed the association between different BK viremia cutoffs and the development of hemorrhagic cystitis, defined as at least macroscopic hematuria. Subjects with a peak plasma BK viral load 1 to 9999 copies/mL had an adjusted hazard ratio of 4.2 (95% confidence interval (CI), 1.3 to 13.7) for the development of hemorrhagic cystitis. Those with peak BK viremia >100,000 copies/mL had an adjusted hazard ratio of 116.8 (95% CI, 12 to 1136) for cystitis. Other independent risk factors for hemorrhagic cystitis included age >7 years and HHV-6 viremia. Neither graft-versus-host disease nor achieving engraftment increased the risk for cystitis. If therapeutic strategies are found to be effective, these observations may support screening for BK viremia after HSCT, as currently recommended for other DNA viruses.
authors.affiliation: Division of Nephrology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. laskinb@email.chop.edu
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Laskin
authors.forename: Michelle
authors.initials: M
authors.lastname: Denburg
authors.forename: Susan
authors.initials: S
authors.lastname: Furth
authors.forename: Donna
authors.initials: D
authors.lastname: Diorio
authors.forename: Jens
authors.initials: J
authors.lastname: Goebel
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.forename: Sonata
authors.initials: S
authors.lastname: Jodele
mesh_terms: D000293:Adolescent; D001739:BK Virus / Q000302:isolation & purification; D002648:Child; D015331:Cohort Studies; D003556:Cystitis / Q000209:etiology / Q000821:virology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006470:Hemorrhage / Q000209:etiology / Q000821:virology*; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D014184:Transplantation, Homologous; D014766:Viremia / Q000821:virology
keywords: BK virus; Hemorrhagic cystitis; Pediatrics; Transplantation