busulfan, high-dose cyclophosphamide or ifosfamide, allogeneic SCT, transplantation from unrelated donors, and graft-versus-host disease (GVHD) are all.
LETTER TO THE EDITOR
Intravesicular Cidofovir for the Management of BK VirusAssociated Cystitis Hemorrhagic cystitis (HC) is a complication of hematopoietic stem cell transplantation (SCT), occurring in 10% to 70% of transplant recipients [1]. Intensive preparative regimens, especially those including busulfan, high-dose cyclophosphamide or ifosfamide, allogeneic SCT, transplantation from unrelated donors, and graft-versus-host disease (GVHD) are all factors that may contribute to the development of HC [2-4]. The frequent finding of BK viral particles in the urine of patients with postengraftment HC also implicates this agent in the pathogenesis of postengraftment HC [4,5]. BK virus (BKV) is a human polyomavirus, a nonenveloped virus with circular, double-stranded DNA. Approximately 80% of adults are seropositive, as exposure to BKV commonly occurs in early childhood. The reactivation of latent BKV in the kidney is thought to lead to the development of late-onset HC in hematopoietic stem cell transplant patients, most commonly within the first 2 months after transplant. Prophylaxis and treatment of BKV-associated cystitis has been attempted with agents such as mesna, quinolones, leflunomide, and the use of hyperhydration or bladder irrigation; however, none are particularly effective in treating the viruria or in diminishing cystitis-related symptoms. Cidofovir (CDF) has been shown to have both in vitro and in vivo antiviral activity against polyomaviruses [6,7]. Reports of intravenous CDF’s efficacy in BKV-associated HC were associated with excessive toxicity, especially renal insufficiency. Intravesicular installation of CDF was first reported in 2005 for the management of adenovirus associated HC [1]. In this report we describe our favorable experience with the use of intravesicular CDF for the treatment of BKV-associated HC. Patients were initiated on treatment with intravesicular CDF if, in addition to BK viruria, they experienced hematuria, dysuria, or urinary urgency. A dose of 5 mg/kg body weight was diluted in a 60-mL syringe with 0.9% sodium chloride and instilled into the bladder via a Foley catheter. If the patient had an indwelling catheter, the catheter was clamped following instillation of CDF for 1 hour to facilitate exposure of drug to the bladder wall. This was repeated daily for 2 days if the catheter remained in place. In patients without need of an indwelling catheter, the
Foley catheter was removed immediately after drug instillation and patients were permitted to urinate as needed. Doses were repeated weekly until resolution of symptoms. A total of 6 patients, 5 matched unrelated donor (MUD), 1 matched related donor (MRD), have been treated thus far. All were recipients of allogeneic SCTs, and presented with symptoms of cystitis while having detectable levels of BKV in the urine. Symptoms included dysuria in 1, urinary urgency in 2, and hematuria in 3 patients. Following initiation of CDF therapy, all 6 patients experienced resolution of their cystitis symptoms. Two patients had resolution of symptoms with a single dose, whereas 3 had resolution of symptoms after 2 weekly doses. Urine BK viral loads were measured in 4 patients, and the response was variable; 3 had decreases in viral loads, whereas 1 had a marked increase despite resolution of symptoms. None of the patients developed renal toxicities attributable to CDF therapy, and other than mild reports of pain associated with the instillation and retention of the product in the bladder, the treatment was well tolerated. In summary, this report summarizes our favorable experience with the first series of patients treated with intravesicular CDF for BKV-associated HC. Treatment was generally well tolerated, and appears to hold potential for the symptomatic improvement of cystitis. REFERENCES 1. Fanourgiakis P, Georgala A, Vekemans M, et al. Intravesicular instillation of cidofovir in the treatment of hemorrhagic cystitis caused by adenovirus type 11 in a bone marrow transplant recipient. Clin Infect Dis. 2005;40:199-201. 2. Erard V, Storer B, Corey L, et al. BK virus infection in hematopoietic stem cell transplant recipients: frequency, risk factors, and association with postengraftment hemorrhagic cystitis. Clin Infect Dis. 2004;39:1861-1865. 3. Russell SJ, Vowels MR, Vale T. Haemorrhagic cystitis in paediatric bone marrow transplant patients: an association with infective agents, GVHD, and prior cyclophosphamide. Bone Marrow Transplant. 1994;13:533-539. 4. Leung AYH, Mak R, Lie AKW, et al. Clinicopathological features and risk factors of clinically overt haemorrhagic cystitis complicating bone marrow transplantation. Bone Marrow Transplant. 2002;29:509-513. 5. Arthur RR, Shah KV, Baust SJ, et al. Association of BK viruria with hemorrhagic cystitis in recipients of bone marrow transplants. N Engl J Med. 1986;315:230-234. 6. Held TK, Biel SS, Nitsche A, et al. Treatment of BK virusassociated hemorrhagic cystitis and simultaneous CMV reactivation with cidofovir. Bone Marrow Transplant. 2000;26:347-350. 7. Andrei G, Snoeck R, Vandeputte M, et al. Activities of various compounds against murine and primate polyomaviruses. Antimicrob Agents Chemother. 1997;41:587-593.
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Kamakshi V. Rao Larry W. Buie University of North Carolina Hospitals, Department of Pharmacy, Chapel Hill, North Carolina
Thomas Shea Don A. Gabriel Terrance Comeau Robert Irons Jonathan Serody
Biol Blood Marrow Transplant 15:391-392, 2009
Lineberger Comprehensive Cancer Center, UNC Hospitals, Chapel Hill, North Carolina
Barbara Eron UNC Healthcare, Department of Nursing, Chapel Hill, North Carolina
Biol Blood Marrow Transplant 15: 391-392 (2009) Ó 2009 American Society for Blood and Marrow Transplantation doi:10.1016/j.bbmt.2008.12.490
