ORIGINAL ARTICLE Low-dose cidofovir treatment of BK virus-associated hemorrhagic cystitis in recipients of hematopoietic stem cell transplant MR Savona 1 , D Newton 2 , D Frame 3 , JE Levine 4 , S Mineishi 4 and DR Kaul 5 1 Division of Hematology–Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; 2 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; 3 College of Pharmacy, Ann Arbor, MI, USA; 4 Blood and Bone Marrow Transplant Program, Division of Hemato–Oncology, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA and 5 Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA In recipients of hematopoietic stem cell transplants (HSCTs), BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC). In our institution, HSCT recipients with BKV-associated HC are treated with 1 mg/kg of cidofovir weekly. We identified HSCT recipients with BKV-associated HC, treated with weekly cidofovir. Microbiological response was defined as at least a one log reduction in urinary BKV viral load; clinical response was defined as improvement in symptoms and stability or reduction in the grade of cystitis. Nineteen allogeneic HSCT patients received a mean of 4.5 weekly doses of cidofovir. HC occurred at a mean of 68.7 days after transplant. A clinical response was detected in 16/19 (84%) patients, and 9/19 (47%) had a measurable microbiological response (8/10 nonresponders had a BKV viral load above the upper limit of the assay before treatment). Fourteen out of nineteen (74%) patients had no significant increase in serum creatinine. Five patients with renal dysfunction resolved after completion of the therapy and removal of other nephrotoxic agents. We conclude that weekly low-dose cidofovir appears to be a safe treatment option for BKV-associated HC. Although the efficacy of low-dose cidofovir is not proven, a prospective trial is warranted. Bone Marrow Transplantation (2007) 39, 783–787; doi:10.1038/sj.bmt.1705678; published online 16 April 2007 Keywords: cidofovir; BK virus; hemorrhagic cystitis Introduction BK virus (BKV) is a human polyomavirus acquired in childhood, which remains latent in the genitourinary tract throughout life. 1 BKV has been associated with ureteral stenosis and graft failure in renal transplant recipients, and in 1986 Arthur et al. 1,2 reported an association between BKV viruria and hemorrhagic cystitis (HC) in recipients of bone marrow transplants. HC complicates the course of 7–40% of recipients of hematopoietic stem cell transplants (HSCTs); early onset disease is probably secondary to the conditioning regimen and later onset disease has been associated with viral pathogens. 1,3–6 Polymerase chain reaction (PCR) can detect BKV in up to 95% of patients at some point after allogeneic HSCT 7 and this has been used for diagnosis and for monitoring during treatment of the disease. 5,7–9 Most of these patients do not develop clinically significant HC, but patients with higher viral loads in the urine or plasma as assessed by quantitative PCR appear to be at increased risk of developing HC. 6–10 Cidofovir (HPMPC) is a cytosine derivative of an acyclic nucleoside–phosphonate analogue, which has broad-spec- trum activity against many DNA viruses including cytomegalovirus (CMV), adenoviruses and polyoma- viruses. 11,12 Low-dose cidofovir (0.25–1.5 mg/kg) has been used successfully in the management of BKV nephro- pathy. 13–16 Although no standard treatment of BKV- associated HC exists, others have described previously the use of intravenous cidofovir at varying doses in HSCT patients with late-onset HC with variable results. 4,5,17–19 Given the paucity of established treatment options, low- dose cidofovir (1 mg/kg) without probenicid has been given weekly at our institution for BKV-associated HC. In efforts to determine if further study of low-dose cidofovir therapy for BKV-associated HC is warranted, the safety profile and the microbiological and clinical outcomes with use of this regimen were investigated. Methods On receipt of approval from the Institutional Review Board, we reviewed the records of all adult HSCT patients at the University of Michigan between April 2003 and May 2004. All adult patients (ageX18 years) with HC, who received at least three doses of cidofovir and had urinary qPCR BKV determinations before and less than 2 weeks Received 13 December 2006; revised 6 March 2007; accepted 15 March 2007; published online 16 April 2007 Correspondence: Dr DR Kaul, Division of Infectious Diseases, University of Michigan Medical Center, Ann Arbor, MI 48109, USA. E-mail: kauld@umich.edu Bone Marrow Transplantation (2007) 39, 783–787 & 2007 Nature Publishing Group All rights reserved 0268-3369/07 $30.00 www.nature.com/bmt