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BK polyomavirus-associated haemorrhagic cystitis (BKHC) is a complication after allogeneic stem cell transplantation, which can occur in 5-60% of the cases. BK viruria alone can also occur in up to 100%. BKHC can lead to severe morbidity in stem cell-transplanted patients, but data about this disease is limited. Consequently, we conducted a prospective unicentric non-interventional trial on BKHC as well as BK viruria after first adult allogeneic stem cell transplantation with a follow-up time of 1 year after inpatient treatment. Between November 2013 and December 2015, we were able to include 40 adult patients with a mean age of 52.8 years. Twenty-seven (67.5%) of these patients were male and 13 (32.5%) were female. Acute myeloid leukaemia was the most frequent underlying disease (n = 15; 37.5%). Only 1 patient developed BKHC during inpatient treatment (n = 1; 2.5%), but BK viruria was frequent (n = 11; 27.5%) during inpatient treatment as well as in the follow-up time (n = 14; 35%). Interestingly, BK viruria was significantly associated with mucositis (p = 0.038) and number of transfused platelet concentrates (p = 0.001). This unexpected association will be discussed and needs further investigation., (© 2019 S. Karger AG, Basel.)

Introduction: BK polyomavirus can lead to hemorrhagic cystitis (BKPyV-HC) in allogeneic stem cell transplantation and therefore to increased morbidity. No causal therapy has been established yet. Cidofovir (CDV) is a nucleotide analog of cytosine that is active against various DNA viruses and it has been described for therapy of BKPyV-HC using 2 admission routes: intravenous and intravesical., Methods: We performed a systematic review regarding the comparison of intravenous or intravesical cidofovir in the treatment of BKPyV-HC following adult allogeneic stem cell transplantation. Since there is a lack of randomized controlled trials, we considered all kinds of studies for this review. Due to heterogeneity of the data, we were not able to perform a meta-analysis, so the results are shown descriptively., Results: The literature search for primary studies yielded 232 results. Finally, 9 studies where considered which included a total of 189 adult patients with BKPyV-HC after allogeneic stem cell transplantation. We could only identify retrospective studies for this review. A total of 172 patients received intravenous CDV, 17 patients received intravesical CDV, and 2 patients received CDV in both admission routes. In 68.0% of the cases, a complete response for intravenous CDV was documented and in 88.2% for intravesical CDV. Interestingly, no kidney toxicity was mentioned in intravesical CDV. 9.3% of the intravenously treated patients had renal failure., Conclusion: There is only weak evidence for the use of CDV. The intravesical admission route should be further investigated because of a good toxicity profile., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

There are no epidemiological data on BK virus associated hemorrhagic cystitis (BKHC) in adult allogeneic stem cell transplantation in Germany available and associations with clinical conditions like GvHD are controversially discussed. Therefore, we conducted a nationwide survey among haematologists and urologists about this disease. We developed two questionnaires, one for haematologists (26 items) and one for urologists (20 items) concerning BKHC in adult allogeneic stem cell transplantation with epidemiological data and clinical implications. The survey was sent out at least three times to EBMT registered centres performing at least five transplantations a year, leading to 39 centres. The recruiting time was between January and June 2016. Total response rates were 76.9% among haematologists and 74.4% among urologists. BKHC seems to appear less frequent in this survey than it is described in the literature. Six deaths in the last 5 years due to this disease have been reported. Interestingly, haematologists as well as urologists mostly think that local therapy is most effective while 50.0% stated that there is no real effective oral or intravenous medication. Associations with other clinical conditions mentioned were heterogeneous, e.g. transplantation type, CMV reactivation, acute GvHD, nephropathy and worse clinical outcome. There was a significant discrepancy between haematologists and urologist concerning the association with acute GvHD (p = 0.004). We need prospective, multicentric clinical studies to evaluate local therapy and for developing a risk stratification model since this disease can be severe with morbidity and rarely mortality. In our opinion, this should be an interdisciplinary approach.

The BK polyomavirus (BKPyV) has pathogenic relevance especially in immunocompromised patients. No causal therapy has been established yet. Therefore, new therapeutic targets need to be identified in experimental studies. A 3D organotypic cell culture model with primary urothelial cells and fibroblasts was used as infection model. The detection of virus replication was performed with quantitative polymerase chain reaction (qPCR), and immunohistochemistry (IHC) was also used for analysis. Interleukin levels were measured by enzyme‐linked immunosorbent assay (ELISA). Interestingly, the signal transducer and activator of transcription 3 (STAT3) pathway seems to be activated during infection with BKPyV, for example phosphorylated STAT3 is significantly (P < 0.0001) elevated on day 6 following infection. Therefore, we performed ELISAs for involved interleukins in STAT3 pathway. Interleukin 11 (IL‐11) was significantly (P = 0.026) elevated at day 9. Subsequently, 3D cultures were treated with IL‐11 neutralizing antibody. At day 9 following infection, the median virus replication rate is 4.4 × 106 copies/ml. The difference to replication rate without treatment was significantly lower at day 6 (P < 0.0001) and at day 9 (P < 0.0001), respectively. STAT3 pathways seem to be involved during BKPyV infection and need further investigation in experimental studies. A very promising target for treatment might be IL‐11. [ABSTRACT FROM AUTHOR]

Every year 50,000 patients receive a stem cell transplantation worldwide, but there is lack of data pertaining to urological complications. Methods: We performed a retrospective analysis of all adult patients undergoing their first allogenic stem cell transplantation from January 2011 to June 2013 in our institution. Statistical tests performed were Pearson's correlation, chi-square testing and logistic regression using SPSS 22.0. Results: We identified 39 patients (22 males, 17 females). Twenty four patients (61.5%) had a urological complication. Most frequent urologic complications were bacterial urinary tract infection (n = 13; 33.3%), acute renal failure (n = 6; 15.4%) and BK virus-associated haemorrhagic cystitis (n = 5; 12.8%). BK viruria was detected in 12 patients (30.8%). We observed an association of creatinine increase (about 20 µmol/l at time of onset of BK viruria) with BK viruria (Pearson's correlation 0.64; p = 0.01), and BK viruria is significantly linked to acute renal failure (Pearson's correlation 0.35; p = 0.029). In univariate regression, BK viruria is significantly linked to urological complication (p = 0.025). Conclusions: We suggest that BK virus infection during stem cell transplantation can lead to BK virus associated nephropathy, which is so far only known from patients after kidney transplantation. [ABSTRACT FROM AUTHOR]