title: Incidence and risk factor of hemorrhagic cystitis after allogeneic transplantation with fludarabine, busulfan, and anti-thymocyte globulin myeloablative conditioning.
abstract: BACKGROUND
  Hemorrhagic cystitis (HC) is a complication of allogeneic stem cell transplantation (SCT), associated with factors such as BK polyomavirus reactivation, age, conditioning regimen, and presence of graft-versus-host disease (GVHD). The incidence and impact of HC in patients receiving fludarabine (Flu), busulfan (Bu), and anti-thymocyte globulin (ATG) conditioning is unknown.
  
  
  METHODS
  We conducted a case-control study of patients undergoing SCT at our center between January 1, 2003 and Dec 31, 2012, to determine the incidence of HC and its effect on patient outcomes including overall survival (OS), relapse, non-relapse mortality (NRM), GVHD, and healthcare resource use.
  
  
  RESULTS
  In total, 94 cases of HC were identified and matched to controls based on age, donor type, disease type, and disease status at transplantation. The total incidence of HC was 17.7% (117 of 661 patients). Cases had a higher rate (43.6% vs 27.1%, P=.0394) of acute GVHD (Grade II-IV), and chronic GVHD requiring systemic steroids (34.9% vs 18.6%, P=.004). Male gender was found to be a risk factor (hazard ratio [HR]=1.725, P=.017). OS and progression-free survival did not differ between cases and controls (OS HR=1.128, 95% confidence interval [CI] 0.7807-1.639; progression-free survival HR=0.8809, 95% CI 0.6320-1.234), however the rate of NRM was higher in cases (HR=1.632, 95% CI 1.007-2.830). Median length of hospitalization was longer for patients with HC than matched controls (65.5 days vs 40.5 days, P<.0001).
  
  
  CONCLUSIONS
  HC is common in patients undergoing allogeneic SCT with FluBuATG conditioning, and affects the duration of hospitalization. Rate of GVHD is higher among patients with HC. While OS is not affected, an association was seen with higher NRM in our study. Improvement in treatment for HC may lead to reductions in morbidity and healthcare resource utilization.
authors.affiliation: Division of Hematology and Hematologic Malignancies, University of Calgary, Calgary, AB, Canada.
authors.forename: Wilson
authors.initials: W
authors.lastname: Lam
authors.affiliation: Division of Hematology and Hematologic Malignancies, University of Calgary, Calgary, AB, Canada.
authors.forename: Jan
authors.initials: J
authors.lastname: Storek
authors.affiliation: Departments of Oncology and Community Health Sciences, University of Calgary, Calgary, AB, Canada.
authors.forename: Haocheng
authors.initials: H
authors.lastname: Li
authors.affiliation: Division of Hematology and Hematologic Malignancies, University of Calgary, Calgary, AB, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Geddes
authors.affiliation: Division of Hematology and Hematologic Malignancies, University of Calgary, Calgary, AB, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Daly
mesh_terms: D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001739:BK Virus / Q000302:isolation & purification; D002066:Busulfan / Q000627:therapeutic use; D016022:Case-Control Studies; D003556:Cystitis / Q000453:epidemiology* / Q000821:virology; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D027601:Polyomavirus Infections / Q000453:epidemiology* / Q000821:virology; D012008:Recurrence; D012307:Risk Factors; D012737:Sex Factors; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods; D014184:Transplantation, Homologous / Q000009:adverse effects; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000961:Antilymphocyte Serum; D019653:Myeloablative Agonists; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: BK virus; cystitis; graft-versus-host disease/complication; hematopoietic stem cell transplantation; polyomavirus infections/complications