Sequential vidarabine infusion in the treatment of polyoma virus-associated acute haemorrhagic cystitis late after allogeneic bone marrow transplantation

Abstract

Summary:Late onset haemorrhagic cystitis (HC) occurs in 20-30% of allogeneic bone marrow transplant patients. Human polyomavirus BK (BKV) (or less frequently adenovirus) may be involved in the pathogenesis of viral HC and can represent a serious post-transplant complication. Diagnosis and treatment of viral HC can be difficult and has an uncertain outcome. We report the efficacy of sequential vidarabine in the treatment of a patient with severe BKV-associated HC, despite the delay in implementing therapy. Bone Marrow Transplantation (2000) 25, 319-320. Keywords: BK virus; haemorrhagic cystitis; sequential vidarabine infusion Late-onset haemorrhagic cystitis (HC) occurs in 20-30% of bone marrow transplant (BMT) patients. 1,2 A strong association has been observed between HC and reactivation of the human polyomavirus BK, with viral shedding in the urine. 2,3 Less frequently, involvement of adenovirus infection in HC has also been reported. 4 However, urinary shedding of BKV and of adenoviruses (among others) may frequently be asymptomatic. Urinary shedding of BKV or of adenovirus may be demonstrated by the Papanicolau stain allowing detection of inclusion bodies and by transmission electron microscopy (TEM) allowing observation of viral particles in the urinary sediments, 5 as well as by virus isolation in cell cultures. However, the use of DNA hybridisation assays with labeled probes and especially of PCR has greatly improved the diagnosis of such infections. 2,3 Among the therapeutic approaches that have been adopted against viral HC, vidarabine has been reported to be active against double-stranded DNA viruses including human BKV. 6 Here, we describe the successful use of vidarabine in the treatment of a BKV patient with severe haemorrhagic cystitis. Case reportA 48-year-old man with acute myeloid leukaemia (FAB M6) in complete remission received an allogeneic BMT from his HLA-identical brother. Conditioning was with busulphan 4 mg/kg p.o. in divided doses daily for 4 days (total dose 16 mg/kg) plus cyclophosphamide 50 mg/kg once daily i.v. on days 5-8 (total dose 200 mg/kg). Prophylaxis of acute acrolein-induced haemorrhagic cystitis was with continuous infusion of mesna and hyperhydratation. Graft-versus-host disease (GVHD) prophylaxis comprised cyclosporin and a short course of methotrexate. Bone marrow transplant was carried out without significant complications. Marrow engraftment occurred at day +18 posttransplant. The patient was discharged on day +35 after BMT, with no transfusion requirement.On day +60 he was re-admitted with severe diarrhoea. Cytomegalovirus (CMV) antigenemia was concomitantly detected (47 cells). As routine faecal cultures for bacteria, fungi and viruses were negative, the diarrhoea was thought to be related to GVHD. High doses of steroids and gancyclovir at a dose of 5 mg/kg twice daily i.v. together with total parenteral nutrition (TPN) led to improvement in the clinical situation and an improvement in the CMV antigenemia (0-2 cells). On day +66, the patient started to experience...

Selective embolization of the internal iliac arteries for the treatment of severe hemorrhagic cystitis following hematopoietic SCT

“…As some viruses are detected in blood and urine samples in LOHC, the administration of antiviral agents has been much tried in recent years, including vidarabine, 14 ribavirin, 15 ganciclovir 16 or cidofovir; 17 however, it is rather difficult for the specific choice of antiviral agents to any HC patient. Ganciclovir prophylaxis is thought to be effective when given to all CMV-positive patients or to patients who were considered at high risk for CMV disease on the basis of a positive surveillance culture.…”

“…2,13 Encouraging results with antiviral agents have been published; however, there is no evident proof in a large number of patients and mainly improve clinical symptoms. [14][15][16][17] The use of formalin, alum, prostaglandin E1, estrogens, FVIIa, factor XIII, hyperbaric oxygen treatment, intravesicular sodium hyaluronate, recombinant human epidermal growth factor or recombinant human GM-CSF has been described, but their efficacy remains controversial. [18][19][20][21][22][23][24][25][26][27] Severe HC may also require surgical treatment with cystoscopy and cauterization, and even cystectomy when previous methods have failed, 28 but it is limited by the disadvantage of operation.…”

CMV reactivation induced BK virus-associated late onset hemorrhagic cystitis after peripheral blood stem cell transplantation

“…However, BK virus could still be detected in the urine after recovery as has been reported in the literature. [3][4][5] In both cases, GVHD preceded the HC and the immunosuppressive therapy could have had a role in the reactivation of both viruses. GVHD is considered a risk factor for the development of HC by several authors.…”

“…Several studies have demonstrated that reactivation of the BK polyomavirus is an important pathogen in the development of HC post BMT. [2][3][4][5] An association between reactivation of CMV and late-onset BK virus-associated HC was recently described in recipients of allogeneic BMT 8 and a trend towards a higher incidence of HC in patients with reactivation of CMV was described in T celldepleted BMT recipients. 7 BK virus and JC virus are members of the human polyomaviruses, and each is 70% homologous with the other.…”

“…[2][3][4][5] Association of CMV infection with HC was described by Spach et al 6 and a trend towards a higher incidence of HC in patients with reactivation of CMV was reported in a group of patients receiving T cell-depleted allografts. 7 Recently, a case of BK virus-associated HC and simultaneous CMV reactivation was described which was successfully treated with cidofovir directed against both the BK virus and the CMV.…”