ORIGINAL ARTICLE A prospective study of BK-virus-associated haemorrhagic cystitis in paediatric patients undergoing allogeneic haematopoietic stem cell transplantation S Cesaro 1 , C Facchin 2 , G Tridello 1 , C Messina 1 , E Calore 1 , MA Biasolo 3 , M Pillon 1 , S Varotto 1 , A Brugiolo 1 , C Mengoli 3 and G Palu` 3 1 Pediatric Hematology Oncology, Department of Pediatrics, University of Padova, Padova, Italy; 2 Infectious Diseases of Pediatric Immunocompromised Host, Department of Pediatrics, University of Padova, Padova, Italy and 3 Department of Histology, Microbiology and Medical Biotechnology, University of Padova, Padova, Italy We investigated the incidence, risk factors and outcome of haemorrhagic cystitis (HC) in paediatric patients undergoing HSCT and the predictive value of BK viruria and viraemia for developing HC. Over a period of 54 months, 74 patients were recruited. The cumulative incidence of HC was 22%. Among 15 patients prospectively monitored for BK viruria and viraemia, four patients developed HC of grade XII. This group, which had two consecutive BK positive samples, showed a sensitivity of 100%, a specificity of 82%, a positive predictive value of 67%, and negative predictive value of 100% for developing HC. Analysed by a receiver–operator characteristic curve (ROC), a urine BK load 49  10 6 genomic copies/ml had a sensitivity of 95% and specificity of 90%; while a blood BK load 41  10 3 genomic copies/ml had a sensitivity of 40% and a specificity of 93% for HC, respectively. In univariate analysis, BK positivity was the only factor significantly associated with HC. After a median follow-up of 1.8 years, patients with HC showed a lower overall survival, 40 vs 65%, P 0.01, and a lower event-free survival, 42 vs 62%, P 0.03, compared to patients without HC. We conclude that BK detection in urine and/or plasma is a specific predictor for developing HC. Bone Marrow Transplantation (2008) 41, 363–370; doi:10.1038/sj.bmt.1705909; published online 5 November 2007 Keywords: paediatric; malignancy; BK virus infection; haemorrhagic cystitis; haematopoietic stem cell transplant- ation Introduction Haemorrhagic cystitis (HC) is a frequent cause of morbidity after allogeneic stem cell transplantation (HSCT), with a reported incidence between 3.6 and 76%. 1–4 BK virus, a human polyoma virus (HuPyV), is usually acquired during infancy as an asymptomatic infection, although it has been associated with urinary tract diseases by some authors. 5,6 The primary infection results in viral latency in renal tubular epithelial and urothelial cells, but asymptomatic BK viruria has been found in 5% to 460% of healthy individuals. 7,8 In recent years, BK virus reactivation has been asso- ciated with the occurrence of late-onset HC after HSCT, 9–11 although other concurrent factors seem to play a role such as acute GVHD, 12,13 an unrelated donor 14 and myelo- ablative conditioning regimen. 15 Other authors have found that adenovirus is involved in HC post-HSCT, especially in Japanese patients. 16 The determination of BK load by quantitative PCR has been shown to increase the specificity and positive predictive value of BK detection in HSCT patients with HC; in particular, a BK load in urine of 410 6 copies/ml and a BK load in plasma of 410 3–4 copies/ml have been shown to be significantly associated with the development of HC. 3,13,15–18 Importantly, the paediatric data published so far have mainly addressed the epidemiological aspects and analysed the risk factors, 1,19,20 while data on the association between BK viral infection and HC post-HSCT are more limited. 11,17,21 We report the results of a prospective study on the incidence of late-onset HC, together with risk factors, and also report the sensitivity, specificity, and positive and negative predictive values of BK viruria and viraemia for developing HC, in paediatric onco-haematological patients undergoing allogeneic HSCT. Materials and methods The main objective of the study was late-onset HC defined as any HC occurring between day þ 2 and day þ 100 post-HSCT. 1 Received 18 June 2007; revised 6 September 2007; accepted 24 September 2007; published online 5 November 2007 Correspondence: Dr S Cesaro, Pediatric Hematology Oncology, Department of Pediatrics, University of Padova, Via Giustiniani 3, Padova 35128, Italy. E-mail: simone.cesaro@unipd.it Bone Marrow Transplantation (2008) 41, 363–370 & 2008 Nature Publishing Group All rights reserved 0268-3369/08 $30.00 www.nature.com/bmt