BACKGROUND: Viruria is frequently detected in patients who have had hemorrhagic cystitis (HC) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Urinary viruses, especially BK virus, have been suggested as a cause of HC following allo-HSCT, therefore antiviral therapy is emerging as a therapeutic approach for its treatment. METHODS: Adult HC patients who underwent allo-HSCT from January 2005 to March 2006 at a single institution were enrolled. We performed a PCR-based assay for BK virus, JC virus, and CMV virus in urine obtained from the patients to determine the incidence of viruria, and the type of virus detected in the urine, and the effect of treatment with cidofovir on HC. RESULTS: Of 155 patients that received allo-HSCT during the study period, 22 (14.2%) experienced HC. A viral study of urine obtained from 19 of these 22 patients revealed that 16 (84.2%) had viruria. Eleven patients had grade III-IV HC, 5 of which were treated with intravenous cidofovir. Three of the HC patients who underwent treatment responded to cidofovir, 1 had no response, and 1 had a complete response followed by recurrence. CONCLUSION: Most adult HC patients (84.2%) had viruria following allo-HSCT, however the response rate to antiviral therapy with intravenous cidofovir for the treatment of high grade HC (grade III-IV) was 80%. Therefore, antiviral therapy should be considered if high grade HC does not respond to hyperhydration and transfusional support.
Adult* ; BK Virus ; Cystitis* ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Incidence ; JC Virus ; Recurrence

Posttransplantation lymphoproliferative disease (PTLD) is an important form of posttransplant malignancy and is typically associated with Epstein-Barr virus (EBV). Progressive multifocal leukoencephalopathy (PML) is a demyelination disease caused by infection of the John Cunningham (JC) virus. Both PTLD and PML occur in the setting of an immunosuppressive state. Differentiating PTLD from PML is important because PTLD can be treated by reducing immunosuppressant agents or anti-B-cell antibody therapy. We report a case of EBV-related PTLD in a patient with latent JC virus.
Demyelinating Diseases ; Herpesvirus 4, Human ; Humans ; JC Virus ; Leukoencephalopathy, Progressive Multifocal ; Viruses

OBJECTIVE: The ubiquitous human polyomavirus, JC virus(JCV) is the etiologic agent of the fatal demyelinating central nervous system(CNS) disease, progressive multifocal leukoencephalopathy(PML). Recent studies have reported the detection of the JCV in samples derived from several type of human neural tumors and suggested the possible association of JCV with CNS tumors. Here we report for the first time, the presence of JCV in Korean glioblastoma multiforme(GM) patients. METHODS: Two Korean GM patients were assayed for JCV. To detect JCV, we performed immunohistochemical analysis using anti-JCV and anti-glial fibrillary acidic protein(GFAP) serum and polymerase chain reaction(PCR) using primers. RESULTS: JCV antigen was detected in cytoplasm abundantly in cells of this tumor case. Also, GFAP immunoreactivity was predominantly observed in cytoplasm of the cells that were morphologically bizarred appearing astrocytes in GM. In addition, both of the large T antigen gene and the VP1 gene were detected and this result correspond with previous result of immunohistochemistry. CONCLUSION: Although it is not certain that GM is associated with the JCV, we are attempted to elucidate the possible implication of JCV in the tumorigenesis of certain human malignant gliomas.
Antigens, Viral, Tumor ; Astrocytes ; Brain* ; Carcinogenesis ; Cytoplasm ; Glioblastoma* ; Glioma ; Humans ; Immunohistochemistry ; JC Virus*

BACKGROUND: Hemorrhagic cystitis(HC), a common complication of bone marrow transplantation(BMT), is known to be associated with toxic metabolites of chemotherapy drugs or reactivation of primary virus infections. In this study, we evaluated the association between polyomaviruria and HC in BMT patients. METHODS: Urine specimens of 29 patients with HC after BMT were requested for the detection of polyomavirus by culture and polyomerase chain reaction(PCR). Several clinical parameters were analyzed in relations to the presence of polyomaviruria. For comparison, 19 patients without HC after BMT were involved in this study. RESULTS: Overall, 45 of 558 patients developed HC after BMT, and the incidence of HC was estimated to be 8.1%. Patients group showed significantly high prevalence of BK viruria compared with control group by PCR(72.4% vs 31.6%, P = 0.005). In patients group, BK virus was isolated in 44.8%(13/29) by culture and detected in 72.4%(21/29) by PCR. Results of both methods were agreed in 65.5%(19/29). JC virus was detected in 6.9%(2/29) by PCR. Sex, conditioning regimen, graft-versus-host disease(GVHD), onset time after BMT and duration of hematuria did not show any statistically significant differences between the two groups based on the presence of BK viruria by PCR. CONCLUSIONS: High prevalence of BK viruria in HC patients after BMT suggests the possible association between BK virus and HC. However, we could not find any significant clinical parameters in association with BK viruria.
BK Virus ; Bone Marrow Transplantation ; Bone Marrow* ; Cystitis* ; Drug Therapy ; Hematuria ; Humans ; Incidence ; JC Virus ; Polymerase Chain Reaction ; Polyomavirus ; Prevalence

Progressive multifocal leukoencephalopathy (PML) is a devastating neurological disease observed nearly exclusively in immunocompromised patients. Recently, the introduction of monoclonal antibodies significantly inhibiting the immune system such as rituximab has led to an increase in PML cases. Although rituximab-based immunochemotherapy remains the standard of treatment for chronic lymphocytic leukemia (CLL), the importance of Bruton’s tyrosine kinase inhibitors such as ibrutinib is steadily increasing. However, long-term experiences regarding possible side effects of these new substances are rare. Here, we report the development of eventually fatal PML possibly associated with ibrutinib therapy for CLL after multiple prior treatment lines, including rituximab. To the best of our knowledge, this is the first study to report such findings. Since the last course of rituximab was applied over 3 years ago, it is conceivable that the strong B cell inhibition by ibrutinib led to PML. With increased awareness of this potential side effect, further clinical studies are certainly warranted to evaluate this possible association.
Antibodies, Monoclonal ; Immune System ; Immunocompromised Host ; JC Virus ; Leukemia, Lymphocytic, Chronic, B-Cell* ; Leukoencephalopathy, Progressive Multifocal* ; Protein-Tyrosine Kinases ; Rituximab

OBJECTIVES: John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals. METHODS: The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: “JCV” OR “JC virus” AND “multiple sclerosis” OR “MS” OR “NMO” OR “neuromyelitis optica” AND “prevalence.” These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase. RESULTS: After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%). CONCLUSIONS: The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.
Adolescent ; Adult ; Antibodies ; Brain ; Humans ; JC Virus* ; Leukoencephalopathy, Progressive Multifocal ; Multiple Sclerosis* ; Natalizumab ; Neuromyelitis Optica* ; Polyomavirus ; Prevalence*

Progressive multifocal leukoencephalopathy (PML) is a rare and fatal disease caused by JC virus. We report a case of PML which developed in a 61-year-old female patient with myasthenia gravis (MG) and thymoma. After 6 years of immunotherapy and chemotherapy she presented with hand weakness followed by progressive decline of consciousness. Serial brain MRI showed rapidly progressive multifocal white matter changes. The JC virus DNA was detected on cerebrospinal fluid. This is a third report of PML in MG.
Brain ; Consciousness ; DNA ; Female ; Hand ; Humans ; Immunotherapy ; JC Virus ; Leukoencephalopathy, Progressive Multifocal ; Middle Aged ; Myasthenia Gravis ; Thymoma

OBJECTIVES: John Cunningham virus (JCV) is a polyoma virus that infects humans, mainly in childhood or adolescence, and presents no symptomatic manifestations. JCV can cause progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals, including those undergoing treatment for multiple sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially fatal disease of the brain. The prevalence of JCV antibodies in human serum has been reported to be between 50.0 and 90.0%. The aim of the present study was to review worldwide data on populations of patients with MS and NMO in order to establish the rates of JCV seropositivity in these individuals.METHODS: The present review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used the following search terms: “JCV” OR “JC virus” AND “multiple sclerosis” OR “MS” OR “NMO” OR “neuromyelitis optica” AND “prevalence.” These terms were searched for both in smaller and in larger clusters of words. The databases searched included PubMed, MEDLINE, SciELO, LILACS, Google Scholar, and Embase.RESULTS: After the initial selection, 18 papers were included in the review. These articles reported the prevalence of JCV antibodies in the serum of patients with MS or NMO living in 26 countries. The systematic review identified data on 29,319 patients with MS/NMO and found that 57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody (range, 40.0 to 69.0%).CONCLUSIONS: The median worldwide prevalence of JCV among adults with MS or NMO was found to be 57.1%.
Adolescent ; Adult ; Antibodies ; Brain ; Humans ; JC Virus ; Leukoencephalopathy, Progressive Multifocal ; Multiple Sclerosis ; Natalizumab ; Neuromyelitis Optica ; Polyomavirus ; Prevalence

The first clinical infections with polyomavirus (PV) were demonstrated in 1971, when BK virus was isolated from the urine after a kidney transplant recipient and JC virus from the brain of a patient who died of progressive multifocal leukoencephalopathy. Polyomavirus-associated nephropathy (PVAN) has become an important cause of allograft dysfunction and loss in kidney transplantation since first recognized in kidney transplant recipient with PVAN in 1995. Most cases of PVAN are caused by polyomavirus hominis type 1, known as BK virus and arise while the patient in on triple immunosuppressive combinations, often comprising tacrolimus and/or mycophenolate mofetil plus corticosteroids. Significant progress has been made, particularly in the area of diagnostic methods for PV, facilitating diagnosis, screening and monitoring of PV infection. Definitive diagnosis of PVAN requires allograft kidney biopsy. Immunologic control of PV replication can be achieved by reducing, switching, and discontinuing of the immunusuppressive agents. Cidofovir and leflunomide are used empirically in the treatment of PVAN. However, these antiviral agents are not approved for PVAN. Recently, investigational use at low-dose cidofovir (0.25~0.33 mg/kg intravenously biweekly) without probenecid should be considered for the treatment of cases refractory to decreasedmaintenance immunosuppression. PVAN had a serious consequence of kidney transplantation that increasingly cause for chronic allograft kidney loss. Despite reduction in immuo-suppression, allograft kidney loss occurred in 46% of transplant recipients with PVAN. PVAN recurred in 15% of retransplantations compared with 5% of primary kidney transplantations. However, retransplantation is not contraindicated for transplant recipient in whom a first allograft kidney lost due to PVAN. Recently, preemptive retransplantation can be considered in patients with allograft loss due to PVAN.
Adrenal Cortex Hormones ; Allografts ; Antiviral Agents ; Biopsy ; BK Virus ; Brain ; Diagnosis ; Humans ; Immunosuppression ; JC Virus ; Kidney ; Kidney Transplantation* ; Leukoencephalopathy, Progressive Multifocal ; Mass Screening ; Polyomavirus ; Probenecid ; Tacrolimus ; Transplantation

The JC virus is a widely infected human polyomavirus. Recent foreign researches showed that the JC virus infection is correlated with tumors of nervous system and digestive system, while, and study on the relationship between JC virus infection and gynecological tumor is seldom reported. In this study, we first establish the nucleic acid detection methods and procedures for JC virus and its highly homologous BK virus. The JC and BK viruses infection was evaluated by detect the viral DNA in samples including biopsy tissues, serum as well as urine of myoma of uterus (98 cases), cervical cancer (84 cases), endometrial cancer (40 cases) and ovarian tumor (72 cases) patients. The BK viral DNA positive rate was significantly higher in urine samples than that of blood and biopsy samples, and there is no significant difference of the BK viral DNA positive rate among all patient groups. The JC viral DNA positive rate is almost 0 in serum samples and biopsy. tissues, however, viral DNA positive rate is more than 50% in urine samples. In fibroids group, the JC viral DNA positive rate is up to 65. 3% which is significantly higher than that in other patients groups and healthy control. Further gynecological tumor associated viruses detection showed that only human papilloma virus infection is associated with cervical cancer, the herpes simplex virus, EB virus and cytomegalovirus infection is extremely low in our patient groups. No synergistic effect on gynecological tumor caused by viruses co-infection was observed. Our study showed that JC virus infection is highly related to the pathogenesis of uterine fibroids.
Adult ; Female ; Genital Neoplasms, Female ; virology ; Humans ; JC Virus ; classification ; genetics ; isolation & purification ; Middle Aged ; Polyomavirus Infections ; virology ; Tumor Virus Infections ; virology ; Young Adult