Guideline sources The following summarized guidelines for the evaluation and management of BK polyomavirus- associated hemorrhagic cystitis (BKPyV-HC) are prepared by our editorial team based on guidelines from the European Conference on Infections in Leukaemia (ECIL 2018) and the Kidney Disease: Improving Global Outcomes Foundation (KDIGO 2009). 1 2 Calculator Grading of hemorrhagic cystitis Guidelines 1. Screening and diagnosis Indications for screening: https://web.pathway.md/diseases/recCrN0g15IjpUo0g 1/4 6/29/23, 3:15 AM BK polyomavirus-associated hemorrhagic cystitis Pathway Do not obtain screening for BKPyV-HC in asymptomatic patients at risk following HSCT, as pre- emptive therapy is not established. D Consider screening all kidney transplant recipients for BK virus infection with quantitative serum NAAT C at least: monthly for the first 3-6 months after transplantation C then every 3 months until the end of the first post-transplant year C whenever there is an unexplained rise in serum creatinine C after treatment for acute rejection. C Diagnostic criteria: Diagnose BKPyV-HC based on the clinical and laboratory triad, while also excluding the significant role of other etiologies: clinical symptoms/signs of cystitis, such as dysuria and lower abdominal pain 2 grade hematuria serum BK polyomavirus loads > 7 log10 gEq/mL. B Consider using plasma BK polyomavirus loads > 1,000 gEq/mL in the management and follow- up of triad-positive patients following allogeneic HSCT. C 2. Respiratory support Hyperbaric oxygen therapy: consider offering hyperbaric oxygen therapy aimed at speeding the healing process of the damaged urothelial lining in patients with BKPyV-HC following HSCT. C 3. Medical management Reduction of immunosuppression: As per ECIL 2018 guidelines, insufficient evidence to provide the risk/benefit ratio of reduction of immunosuppression in patients with BKPyV-HC following HSCT. Balance the reduction of immunosuppression with the risk of worsening or triggering acute GvHD. I As per KDIGO 2009 guidelines, consider reducing immunosuppressive medications when BK virus serum NAAT is persistently > 10,000 copies/mL (107 copies/L) in kidney transplant recipients. C Supportive therapy: offer hyperhydration and perform bladder irrigation and platelet transfusions as needed to reduce bleeding and pain in patients with BKPyV-HC following HSCT. B Antiviral therapy: consider administering IV cidofovir until the availability of safe and effective antiviral treatment, recognizing that there is uncertainty of efficacy, the best dose schedule and the need to balance any benefit against its renal side effects. C https://web.pathway.md/diseases/recCrN0g15IjpUo0g 2/4 6/29/23, 3:15 AM BK polyomavirus-associated hemorrhagic cystitis Pathway Agents with no evidence for benefit: insufficient evidence to support the use of intravesical sodium hyaluronate, IV FXIII concentrate, leflunomide, estrogens, mesenchymal cells, and cellular immunotherapy. I 4. Therapeutic procedures Fibrin glue: consider applying fibrin glue aimed at speeding the healing process of the damaged urothelial lining in patients with BKPyV-HC following HSCT. C 5. Preventative measures Prophylaxis: Consider offering hyperhydration C and performing bladder irrigation for BKPyV-HC prophylaxis aiming to reduce urothelial damage, particularly when using myeloablative conditioning based on cyclophosphamide, busulfan and total body irradiation. C Recognize that specific antiviral prophylaxis is not available. Do not use fluoroquinolones given the lack of significant effects on BK polyomavirus replication and hemorrhagic cystitis severity, and the selection of antibiotic resistance. B Clinical findings Symptoms Lab findings Burning on urination serum BK virus deoxyRNA Dysuria Hematuria Penile pain Suprapubic pain Urinary frequency Urinary incontinence Urinary urgency Endoscopic findings Bladder wall telangiectasia References 1. Simone Cesaro, Tina Dalianis, Christine Hanssen Rinaldo et al. ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients. J Antimicrob Chemother. 2018 Jan 1;73 1 12 21. Open https://web.pathway.md/diseases/recCrN0g15IjpUo0g 3/4 6/29/23, 3:15 AM BK polyomavirus-associated hemorrhagic cystitis Pathway 2. Kidney Disease: Improving Global Outcomes KDIGO Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009 Nov;9 Suppl 3 S1 155. Open 3. A Thompson, A Adamson, A Bahl et al. Guidelines for the diagnosis, prevention and management of chemical- and radiation-induced cystitis. J Clin Urol. 2014 Jan;7 1 25 35. Open 4. Jessica H Hannick, Martin A Koyle. Canadian Urological Association Best Practice Report: Pediatric hemorrhagic cystitis. Can Urol Assoc J. 2019 Nov;13 11 E325 E334. Open https://web.pathway.md/diseases/recCrN0g15IjpUo0g 4/4