Bk virus quantitation

After primary infection, the virus enters latency in the host, most likely in the urogenital tract. Asymptomatic reactivation and intermittent shedding of the virus in urine occur spontaneously in immunocompetent and immunosuppressed persons. BK virus replication in the urogenital tract can also present as hematuria, hemorrhagic cystitis, ureteric stenosis and interstitial nephritis.

Persistent viral replication in recipients of renal allografts can cause progressive dysfunction and eventual loss of the transplanted kidney. Test sent to Viracor Eurofins. Test Overview Test Methodology. Test Usage. Test Limitations. Days Set Up. Analytic Time. Consequently, different approaches have been established to increase the purity of virus specific T cells and viral cytotoxicity concomitant with minimizing the alloreactivity.

Table 3 contains different methods used in various articles for generation of VST along with their advantages and disadvantages. Infusion of adoptive virus specific T cells can prevent viral replication and reestablish antiviral immunity in patients not responding to antiviral therapies.

Infusion of adoptive VSTs has been used for almost 30 years. Different methods have been utilized to produce VST against various viruses which reactivated after HSCT and have been associated with remarkable successes. Since VST infusion has been associated with significant improvement in post-transplant complications of these viruses, it is readily applicable to many other viruses include BK and JC polyomaviruses.

In that study, VST were produced by cytokine capture method and transfused into one patient. The patient showed complete resolution of HC without any complication including GVHD, graft rejection or bystander organ toxicity [ 87 ]. The study involved a total of 11 patients, of whom 7 had reactivation of BK virus. After transfusion, 5 and 1 patients achieved complete and partial response, respectively. One patient showed no response to infusion [ 88 ]. Most of the published papers are case reports and have been performed on a small number of patients.

So currently no conclusions can be reached on the efficacy and safety of this approach. In recent years, Mesenchymal stromal cells MSCs have captured significant interest in regenerative medicine because of their potential immunomodulatory effects, low immunogenicity and wound healing abilities [ 89 , 90 ]. They can differentiate into various mesenchymal tissues. It has been shown that they can also reverse tissue toxicity such as hemorrhagic cystitis, because they can directly differentiate into bladder urothelium or indirectly stimulate tissue repair [ 89 , 91 ].

All studies conducted in this setting have uniformly revealed that it is safe to infuse MSCs in humans with no acute toxicity [ 89 , 90 , 92 ]. It causes significant mortality and morbidity. There is still no standard and approved treatment protocol for BKV-HC and it is according to the local standard operating procedures, depending on the cause and severity. Prevention probably is the best treatment of hemorrhagic cystitis.

Preventive measures include urine alkalization, hyperhydration, continuous bladder irrigation and the use of MESNA. Most cases of BKV-HC are mild and self-limited and can be treated with conservative therapies or complimentary options, but refractory patients or severe episodes of BKV-HC may require further measures. Currently, there are no specific antiviral drug with strong evidence of clinical efficacy against BKV. The typical clinical method upon identification of BK viremia is gradual reduction of immunosuppression regimen which may increase the risk of acute rejection and exacerbating GVHD.

Furthermore its long-term consequence is a higher incidence of chronic rejection. Cidofovir, brincidofovir, leflunomide and quinolone antibiotics have been described to affect the virus replication and can be applied as treatment options. However all studies called for further investigations or a need for high-quality prospective randomized controlled trials to describe the optimal treatment strategies following BKV reactivation.

Adoptive cell therapy especially VST therapy is a novel therapeutic method that is currently in early clinical research and can be a logical alternative to conventional treatments. National Center for Biotechnology Information , U. Am J Blood Res. Author information Article notes Copyright and License information Disclaimer.

Address correspondence to: Dr. Tel: ; E-mail: ri. Tel: ; E-mail: moc. Received Jun 28; Accepted Sep This article has been cited by other articles in PMC. Abstract Hematopoietic stem cell transplantation HSCT represents a vital curative choice for many disease. Keywords: BK virus, hemorrhagic cystitis, hematopoietic stem cell transplantation, cidofovir. Introduction Hematopoietic stem cell transplantation HSCT represents a vital curative choice for patients with a large group of malignant disorders such as leukemia and lymphoma, and nonmalignant conditions mainly metabolic diseases and immunodeficiency syndromes.

BK virus pathogenesis, prevalence, diagnosis and risk factors BK virus is a member of the polyoma viridae family. Open in a separate window. Treatment Treatment of hemorrhagic cystitis is according to the local standard operating procedures, depending on the cause and severity [ 6 , 11 ].

Table 2 Clinical trials for HC. Conservative therapy Conservative therapies, also known as supportive approaches or symptomatic therapies, are considered as preventive and the first steps of therapy in most centers. Complimentary options In more severe cases grades 2 and 3 HC , complimentary options described below are used: - Optimization of the hematological homeostasis including the use of clotting factors recombinant factor VIIa or VIII, factor XIII and antifibrinolytic agent aminocapronic acid [ 6 , 11 ].

Surgical procedures In very severe cases, as last step of treatment, urological intervention and surgical management such as bilateral percutaneous nephrostomy tubes with or without ureteral occlusion, selective arterial embolization, cauterization, fulguration and total or partial cystectomy should be considered [ 6 , 11 , 49 ]. Pharmacological treatments Currently, there are no specific antiviral treatments with strong evidence of clinical efficacy against BKV.

Adoptive cell therapy Although pharmacological therapies and prophylactic options are available to treat viral infections, they remain limited and ineffective due in part to drug resistance, drug related toxicities and morbidities notably acute kidney injury and myelosuppression [ 1 , 78 , 79 ]. VSTs The preliminary practices of adoptive T cell transfer were based on nonspecific donor lymphocyte infusions DLIs which led to restoring antiviral immunity with promising results.

Table 3 Different methods for generation of VST. Ultimately expansion of T cells using IL Different practices for the generation of multivirus-specific T cells in one single step have been established. Third-party VST can be utilize for these patients. Mesenchymal stromal cells In recent years, Mesenchymal stromal cells MSCs have captured significant interest in regenerative medicine because of their potential immunomodulatory effects, low immunogenicity and wound healing abilities [ 89 , 90 ].

Disclosure of conflict of interest None. References 1. Adoptive T cell therapystrategies for viral infections in patients receiving haematopoietic stem cell transplantation. Houghtelin A, Bollard CM. Virus-specific T cells for the immunocompromised patient. Front Immunol. Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. Hematopoietic stem cell transplantation: clinical use and perspectives.

Biol Res. Strategies of adoptive T-cell transfer to treat refractory viral infections post allogeneic stem cell transplantation. J Hematol Oncol. Hemorrhagic cystitis in a cohort of pediatric transplantations: incidence, treatment, outcome, and risk factors. Biol Blood Marrow Transplant. Presentation of BK polyomavirus-associated hemorrhagic cystitis after allogeneic hematopoietic cell transplantation.

Blood Adv. Hemorrhagic cystitis after allogeneic hematopoietic cell transplantation: risk factors, graft source and survival. Bone Marrow Transplant. ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients.

J Antimicrob Chemother. Schneidewind L, Neumann T. Comparison of intravenous or intravesical cidofovir in the treatment of BK polyomavirus-associated hemorrhagic cystitis following adult allogeneic stem cell transplantation-A systematic review.

Transpl Infect Dis. BK polyomavirus: clinical aspects, immune regulation, and emerging therapies. Clin Microbiol Rev. Polyoma virus in transplant recipients. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type. Incidence, clinical outcome, and management of virus-induced hemorrhagic cystitis in children and adolescents after allogeneic hematopoietic cell transplantation.

Human polyomavirus reactivation: disease pathogenesis and treatment approaches. Clin Dev Immunol. Polyomavirus BK infection in blood and marrow transplant recipients.

Boothpur R, Brennan DC. Human polyoma viruses and disease with emphasis on clinical BK and JC. J Clin Virol. Hirsch H, Pergam S. Human adenovirus, polyomavirus, and parvovirus infections in patients undergoing hematopoietic stem cell transplantation.

BK-virus BKV - structure, epidemiology and pathogenesis. J Pre Clin Clin Res. Risk factors of BK virus cystitis in haematopoietic stem cell transplantation-a retrospective monocentric study.

Different risk factors related to adenovirus- or BK virus-associated hemorrhagic cystitis following allogeneic stem cell transplantation. High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation. Association between a high BK virus load in urine samples of patients with graft-versus-host disease and development of hemorrhagic cystitis after hematopoietic stem cell transplantation.

J Clin Microbiol. BK virus disease after allogeneic stem cell transplantation: a cohort analysis. Challenges and opportunities in radiation-induced hemorrhagic cystitis. Rev Urol. Clinical effectiveness of hyperbaric oxygen therapy for BK-virus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation. Intravesical application of platelet-rich plasma in patients with persistent haemorrhagic cystitis after hematopoietic stem cell transplantation: a single-centre preliminary experience.

Int Urol Nephrol. Efficacy and safety of ciprofloxacin for prophylaxis of polyomavirus BK virus-associated hemorrhagic cystitis in allogeneic hematopoietic stem cell transplantation recipients. Association of BK virus with failure of prophylaxis against hemorrhagic cystitis following bone marrow transplantation. Application of fibrin glue to damaged bladder mucosa in a case of BK viral hemorrhagic cystitis.

Current applications of fibrin sealant in urologic surgery. Int Braz J Urol. Fibrin glue therapy for severe hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. The early histological effects of intravesical instillation of platelet-rich lasma in cystitis models. Int Neurourol J. Evaluation of three methods of platelet-rich plasma for treatment of equine distal limb skin wounds.

J Equine Vet Sci. Equine idiopathic hemorrhagic cystitis: clinical features and comparison with bladder neoplasia. J Vet Intern Med. Late onset hemorrhagic cystitis in a hematopoietic stem cell recipient: treatment with intravesical hyaluronic acid. Pediatr Transplant. Treatment of post-hematopoietic stem cell transplantation hemorrhagic cystitis with intravesicular sodium hyaluronate. May include disease information, patient result explanation, recommendations, details of testing, associated diseases, explanation of possible patient results.

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