Investigation of Polyomavirus BK in the Late-Onset Hemorrhagic Cystitis Following Hematopoietic Stem Cell Transplantation

Background Late-onset hemorrhagic cystitis (LOHC) is a frequent and sometimes life-threatening complication after hematopoietic stem cell transplantation (HSCT). Our aim in this study is to analyze the risk fators for LOHC after HSCT, then determine the role of polyomavirus BK in the development of LOHC following HSCT.

Methodology 113 patients undergoing HSCT and 30 normal subjects were enrolled in this study. BK virus DNA were detected with PCR in the plasma and urine samples, while cytomegalovirus (CMV) antigen in peripheral blood was identified by immunofluorescence histochemical examination. All patients with LOHC were classified into three groups as grade 1, grade 2 and grade 3–4 by the severity of HC.

Results 22 patients developed LOHC (19.47%), all of them were allogenetic transplants recipients, with a median time of 44 days after HSCT. BK viruria was detected in 50 of all 113 patients following HSCT (44.2%), and no positive BK virema was found at the same time, while CMV virema was detected in 21 patients (18.5%). Of the 22 LOHC patients, 21 were detected BK viruria (95.5%), which was much more than that of non-HC patients (31.9%, P©‚0.01). The first time of BK viruria detection is earlier than the onset time of HC (25.09±16.63 days vs 47.42±29.02 days, P©‚0.01), accompanied with a longer median persistence time than that of HC (6 weeks vs 11 days), no difference was found in the onset and persistence time of HC among all the HC groups of three grades. Both CMV and BKV detection were negative in the control subjects. The occurrences of severe infection (45.5%), CMV reactivation (40.9%) and grade II-IV aGVHD development are much higher in HC group than that of non-HC group(P©‚0.01). Cox’s proportional hazard regression analysis showed that CMV reactivation and the development of grade II-IV acute graft-versus-host disease (GVHD) were associated with the occurrence of BK viruria, while BKV viruria and aGVHD of grade II-IV were independent risk factors of LOHC.

Conclusion BK polyomavirus may contribute to the pathogenesis of LOHC after HSCT, manifested as BK viruria. CMV infection and GVHD could be involved in the occurrence of BKV-related HC.