Monitoring BK virus infection for preemptive treatment in children after hematopoietic stem cell transplantation

Hemorrhagic cystitis due to BK virus (BKV) is a relatively common, serious complication in the early period after hematopoietic stem cell transplantation (HSCT). The purpose of this study was to identify BKV infections in children undergoing HSCT, to assess the incidence of BKV related hemorrhagic cystitis (BKV-HC) and also to describe possible risk factors associated with BKV-HC. A total of 80 pediatric patients who underwent HSCT at our university hospital from January 2020 to October 2023 were retrospectively (65) and prospectively (15) analyzed. BKV DNA was serially tested by quantitative real-time PCR in urine and blood samples of children (median age 7 years) with allogeneic (68) and autologous (12) HSCT. BKV infection was diagnosed in 55 (68,7%) of 80 patients. The incidence of BKV viruria was 67,6% (46) in allogeneic group and 75% (9) in autologous group. High BKV viruria (>107 copies /ml) was observed in 38 (47,5%) patients (47% in allogeneic group and 50% in autologous group). Among 80 patients, BK viremia was detected in 20 (25%) and high viremia (>104 copies /ml) in only 16 (23,5%) patients of allogeneic group. Preemptive treatment was initiated for 38 asymptomatic patients with high BKV viruria to reduce the risk of progression to symptomatic disease. Thus, a potential BKV-HC was prevented in 22 patients. BKV-HC occured in 16 (20%) at a median of 35 days (10-81 days) after HSCT, of which 15 (22%) in allogeneic and 1 (8,3%) in autologous group. It was determined that BKV viruria in two weeks before HC with a median viral load of >5,6x108 copies/ml appears to be predictive for the development of BKV-HC. However BKV viremia was found in only 3 patients before the onset of HC. In addition, statistical analysis showed that age ≥7 years and BKV positivity prior to HSCT in allogeneic group were significantly correlated with HC, while there were no differences between patients with HC and without HC in terms of male gender, graft-versus-host disease, myeloablative conditioning regimen, cytomegalovirus reactivation, peripheral blood transplantation and bone marrow transplantation as probable risk factors for BKV-HC. In conclusion, our findings demonstrated that regular screening for urine BKV DNA load weekly particularly for 3 months after HSCT could be useful for identifying the patients at risk for HC and also allows us to start early preemptive treatment as prevention strategy for BKV-HC that may develop following pediatric HSCT. Keywords: BK virus, hematopoietic stem cell transplantation, hemorrhagic cystitis, real-time PCR