The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD

Abstract

Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic SCT (allo-HSCT). Several risk factors have been suggested including BU-containing myeloablative conditioning, unrelated donors and GVHD, but these have not been consistently reported. We conducted a retrospective study including 339 allo-HSCT recipients between 2009 and 2012. Of 339 patients, 79 (23.3%) developed HC with 2-year cumulative incidence of 24.0% (95% confidence interval, 19.4-28.9). The median onset time was 45 days (range, 16-430) after allo-HSCT. Sixty-two patients (84%) out of 74 evaluated for urine BK virus PCR testing showed a positive result (mean 2.0 × 10 10 copies of DNA per mL). In univariate analysis, myeloablative conditioning, HLA-mismatched donor, CMV viremia and acute GVHD (aGVHD) grade 3-4 were significantly associated with the risk of HC. Multivariate analysis confirmed all associating factors identified in univariate analysis except for HLA-mismatched donor: myeloablative conditioning (hazard ratio (HR) 2.63, P = 0.003), CMV viremia (HR 1.88, P = 0.014) and aGVHD grade 3-4 (HR 1.71, P = 0.029). HC did not affect OS or non-relapse mortality. Symptomatic HC is a frequent complication following allo-HSCT, with a 2-year cumulative incidence of 24.0%. Three clinical factors associated with HC were identified including myeloablative conditioning, CMV viremia and severe aGVHD.

Are the Polyomaviruses BK and JC Associated with Opportunistic Infections, Graft-versus-Host Disease, or Worse Outcomes in Adult Patients Receiving Their First Allogeneic Stem Cell Transplantation with Low-Dose Alemtuzumab?

“…Interestingly, although the question of whether BKPyV is associated with other typical transplantation-related infections like CMV reactivation is controversially discussed, JCPyV has been less investigated. In their retrospective analysis of 339 patients who underwent allogeneic stem cell transplantation, Uhm et al [13] described CMV viremia as a significant risk factor for BKPyV-associated hemorrhagic cystitis, but another study with kidney-transplanted patients under immunosuppression identified CMV as a protecting factor against BKPyV infection [13,14]. We found no significant association of BKPyV and JCPyV with CMV in our patients.…”

Hemorrhagic cystitis after allogeneic hematopoietic cell transplantation: risk factors, graft source and survival

“…HC incidence was 16.6%, in line with other studies. 8, 10, 31 Interestingly, compared to our prior study performed nearly 20 years ago, the incidence of HC has not changed. 20 Male gender was the most important risk factor for developing HC as has been reported in earlier studies of relatively small number of patients 14, 31–33 .…”

“…Several predisposing factors have been reported including transplant type, age at transplantation, presence of graft-versus-host disease (GVHD), donor source, and conditioning regimen components and intensity 1, 12, 19–21 . The effect of HC on survival remains controversial, but its morbidity can be substantial, even in survivors 10, 22 .…”

Urological Complications and BK Virus-Associated Diseases Under Allogenic Stem Cell Transplantation

“…Several risk factors for BK virus-associated haemorrhagic cystitis have been identified so far: in retrospective studies, myeloablative conditioning, CMV viremia, acute GvHD grades 2-4 and in prospective studies, myeloablative conditioning and acute GvHD again [15,16]. However, the questions for proper risk stratification and when urological interventions are needed remain to be answered.…”