Prospective analysis of BKV hemorrhagic cystitis in children and adolescents undergoing hematopoietic cell transplantation

Abstract

BK virus is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic cell transplantation (HCT). Viruses can be found in urine and serum samples of immunocompromised patients. Malignant diseases, age, cell source, day of granulocyte reconstitution, conditioning regimen, or use of total body irradiation may play an important role in BKV epidemiology, development of hemorrhagic cystitis course, and outcome. The aim of this study was to evaluate the incidence, clinical course, and risk factors for BKV-HC in children undergoing HCT. A total number of 133 patients who were prospectively tested for BKV colonization/infection were enrolled into this multicenter analysis. Episodes of BKV-HC occurred in 36/133 (27%) enrolled subjects. In a univariate analysis for BKV-HC incidence, the following factors were significant: age >5 years, peripheral blood transplantation, matched unrelated donor (MUD) transplantation, busulfan-cyclophosphamide-melphalan conditioning regimen, and acute myeloblastic leukemia (AML) diagnosis. Presence of acute graft-versus-host disease (aGVHD) in liver and gut GVHD was a significant risk factor of BKV-HC. No BKV-attributed deaths were reported. In multivariate analysis, the incidence of HC was significantly higher in patients with AML, age >5 years, MUD transplants, and children with GVHD. HC is a frequent complication after HCT among children causes prolonged hospitalization but rarely contributes to death. We identified risk factors of BKV-HC development in children, with focus on aGVHD: we concluded that excessive immune reaction connected with GVHD and immunosuppression drugs might play a pivotal role in the development of BKV-HC.

Biomarkers in the Light of the Etiopathology of IC/BPS

“…In controls, the authors could not detect EBV-RNA [ 39 ]. Also, BK polyoma viruses (BKPyV), which can induce hemorrhagic cystitis [ 40 ], were found in the urine of IC/BPS patients and could play a role in the etiopathology of IC/BPS [ 41 ]. Occult bacterial infection, persisting in macrophage was already demonstrated in endocarditis [ 42 ].…”

Fludarabine–Cyclophosphamide-Based Conditioning with Antithymocyte Globulin Serotherapy Is Associated with Durable Engraftment and Manageable Infections in Children with Severe Aplastic Anemia

“…The incidence of BKV seems to be low among children with SAA after HCT [ 44 ]. In children with malignancies, the incidence of BKV was shown to be 25–62%, and up to 27% patients developed BKV-hemorrhagic cystitis [ 45 ]. Malignant indications were reported in multiple studies to be associated with symptomatic BKV infection, but this can be explained by a more intensive conditioning protocol with uroepithelial damage and intensive immune suppression [ 45 , 46 , 47 ].…”

“…In children with malignancies, the incidence of BKV was shown to be 25–62%, and up to 27% patients developed BKV-hemorrhagic cystitis [ 45 ]. Malignant indications were reported in multiple studies to be associated with symptomatic BKV infection, but this can be explained by a more intensive conditioning protocol with uroepithelial damage and intensive immune suppression [ 45 , 46 , 47 ]. In our cohort, despite BKV replication in 29% of HCT recipients, the infections were asymptomatic and not associated with death.…”

Analysis of incidence and risk factors of the multidrug resistant gastrointestinal tract infection in children and adolescents undergoing allogeneic and autologous hematopoietic cell transplantation: a nationwide study

“…In RIC regimen, fludarabine with either melphalan or low, non-myeloablative doses of busulfan (2 mg/kg) was used. MAC based either on myeloablative doses (12.8–19.6 mg/kg) of busulfan or on total body irradiation (TBI) at a median dose of 12 Gy [ 6 ]. Type of donor, graft source, reconstitution day, and conditioning regimen are presented in Table 1 .…”