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

Abstract

Summary:Hemorrhagic cystitis (HC) is a known complication of stem cell transplantation. In contrast to early-onset HC that is usually attributed to cyclophosphamide and occurs within a few days of infusion, late onset HC is associated with viral infection. In recent years BK virus has emerged as an important causative agent. We describe two patients who developed late onset HC (38 and 92 days post transplant) associated with BK viruria concomitant with CMV reactivation and suggest a possible role of CMV in the process of BK virus DNA replication. Bone Marrow Transplantation (2001) 28, 613-614. Keywords: BK virus-associated hemorrhagic cystitis; CMV reactivation; peripheral blood stem cell transplantation An association between BK viruria and hemorrhagic cystitis (HC) in recipients of bone marrow transplants was first described by Arthur et al. 1 Since then, an increasing number of reports has identified the BK virus as the most common pathogen in late onset HC post BMT.2-5 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. 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. 9 JC virus is a member of the human polyomavirus family which is closely related to BK virus.Based on the interaction between CMV and JC virus (another member of the human polyomavirus family) we suggest an explanation for the temporal association between CMV reactivation and the occurrence of BK virus-associated late-onset HC and emphasize the role of ganciclovir in controlling both infections. Case 1A 4-year-old male with X-linked chronic granulomatous disease underwent peripheral blood stem cell (PBSC) transplantation from his HLA-identical brother in December 1998. The patient had pulmonary aspergillosis and was treated with liposomal amphotericin and granulocyte transfusions as previously described. 10 The conditioning regimen included busulfan, cyclophosphamide and ATG. GVHD prophylaxis consisted of cyclosporine and short course MTX. Both donor and recipient were CMV seropositive.The patient had rapid engraftment and there were no major complications during the transplant period. On day 60 post-transplant, he developed grade III skin GVHD that was treated with high-dose corticosteroids, cyclosporine, ATG and mycophenolate and which gradually resolved. On day 92 post-transplant he developed grade III HC. BK virus was identified in the urine by PCR for early gene using a specific PCR primer pair for BK virus. Reactivation of CMV was detected by positive antigenemia and CMV was also found in the urine culture taken at the onset of HC. Treatment with ganciclovir was initiated along with aggressive hydration, which resulted in resolution of the HC within a month. CMV became negative within 12 days. Case 2A 6.-year-old boy with very slowly re...

Viruria in Adult Hemorrhagic Cystitis Patients Following Allogeneic Hematopoietic Stem Cell Transplantation and Implication of Antiviral Treatment

“…Viruses which have been reported as the cause of HC after HSCT are BK virus, JC virus, adenovirus, CMV, herpes simplex virus, and influenza A virus. [8][9][10][11][12]15) The incidences of each type of virus in urine in this study are similar to that described in a prior report. 1) BK virus was the most common virus detected in HC after HSCT.…”

“…Despite of many different therapies being described, no definitive treatment has been established. Recent studies imply that the important viruses causing late-onset HC after allo-HSCT are BK virus, JC virus, adenovirus, and cytomegalovirus (CMV) virus 1,4,[8][9][10][11][12] and antiviral therapy is emerging as an promising treatment for HC. In this study, the frequency of viruria in adult patients who developed HC after allo-HSCT and the types of virus detected in urine in those patients were analyzed.…”

Polyoma viruria following T-cell-depleted allogeneic transplants using Campath-1H: incidence and outcome in relation to graft manipulation, donor type and conditioning

“…17 This is the first time this has been demonstrated in a prospective study. In half of the patients, virus excretion subsided with achievement of CMV-PCR negativity, and in the other half it persisted for several weeks after this had been achieved.…”

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

“…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.…”