High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation.

BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P=0.028), unrelated donor (P=0.0178), stem cell source (P=0.0001), HLA mismatching (P=0.0022) and BU in conditioning regimen (P=0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P=0.0005) and peripheral blood stem cells (P=0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P=0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (P<0.0001), more RBC (P=0.0003) and platelet transfusions (P<0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at \[euro]2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

Cost-effectiveness of cidofovir treatment of polyomavirus nephropathy in kidney transplant recipients.

BACKGROUND: BK virus nephropathy (BKVAN) causes about 10% of late kidney graft loss. Cidofovir is widely used to treat BKVAN, but the magnitude of the health benefits and costs are largely unknown. We aimed to evaluate the incremental health benefits and costs of cidofovir and immunosuppression reduction compared with immunosuppression reduction alone in kidney transplant patients with BKVAN. METHODS: A probabilistic decision analytic model was developed to simulate a cohort of kidney transplant recipients aged 45 years and above with BKVAN who received cidofovir treatment compared with those who received standard care. The duration of the cycle was 1 year, and the model terminated when all recipients were deceased. RESULTS: Compared with immunosuppression reduction alone, in the base-case, the incremental health benefits of cidofovir were 0.0061 life-years saved (2.2 days), with savings of $20,756 over the lifetime of a transplant recipient. When varying the most influential variables (the probability of response to treatment and graft loss) between best and worst case scenarios, the incremental health outcomes ranged from -0.967 to 1.093 life-years saved, with incremental costs ranging from an extra $27,313 to saving $20,756. CONCLUSIONS: Compared with immunosuppression reduction alone, based on best available data, cidofovir treatment and immunosuppression reduction for BKVAN seem to be cost saving and improves health outcomes. However, because of weak clinical data, particularly around comparative effectiveness, there is still moderate uncertainty in the incremental cost effectiveness. Adequately powered trials are still needed to better define optimal treatment strategies for BKVAN before cidofovir can be recommended strongly as routine therapy.

Cost-efficient screening for BK virus in pediatric kidney transplantation: a single-center experience and review of the literature.

BKVNP is an increasingly recognized cause of graft dysfunction and loss in kidney transplant recipients. Protocols for BKV screening and for the diagnosis of BKVNP are still evolving. PCR-based BKV detection became available at our institution in 2007, when we began using it according to published guidelines. We subsequently reviewed our experience with urine and plasma BKV PCR testing in our pediatric kidney transplant recipient population. We found rates of viruria, viremia, and BKVNP that were similar to the published literature. We also conducted a cost analysis suggesting that urine PCR testing, as used by us, is not cost efficient in the detection of BKV. We conclude that plasma only-based PCR testing for BKV may be sufficient in most clinical settings.

Screening to prevent polyoma virus nephropathy in kidney transplantation: a cost analysis.

Polyoma virus nephropathy is an important cause of graft dysfunction in kidney transplant recipients and screening to prevent disease has been advocated. Although screening incurs new costs, our hypothesis is that savings from less immunosuppression in those with positive screening tests could pay for overall costs of screening. In 134 consecutive recipients, polyoma virus (positive decoy cells) was detected in the urine of 34 (25.4%) individuals over a 2-year follow-up. Of these 34, 11 had a plasma BK PCR of >7700 copies/mL. Immunosuppression was reduced stepwise in these patients until viral loads fell <1000/mL. Overall screening costs (including extra plasma PCR testing) were estimated at $33,450. Those with positive PCR had greater reductions in annual immunosuppression costs by year 2 ($6452 vs. $2799, p = 0.0015) compared to those with negative screens. At the end of the 2-year period, 61% of the screening costs were covered by less immunosuppressant costs. At the end of 30 months there were net savings. In summary, reductions in immunosuppression cover the cost of screening for polyoma viral infection. Longer-term follow-up is needed to ensure patient outcomes remain acceptable.

Case studies in cost effectiveness of molecular diagnostics for infectious diseases: pulmonary tuberculosis, enteroviral meningitis, and BK virus nephropathy.

Pathogen genome amplification is used to detect and identify microorganisms, assess response to therapy, and detect mutations associated with drug resistance. Nucleic acid amplification tests have been shown to be superior to conventional culture-based testing methods in many circumstances. However, the enthusiasm for the technology in clinical laboratories may be decreased by the practical considerations of cost, complexity of the technology, and lack of US Food and Drug Administration-approved tests. The impact of nucleic acid amplification tests on the diagnosis and management of patients with tuberculosis, enteroviral meningitis, and BK virus transplant nephropathy will be examined, with an emphasis on the potential for health care cost savings.

Cost efficiency in the prospective diagnosis and follow-up of polyomavirus allograft nephropathy.

Evaluation of urine cytology (UC) for decoy cells and quantitative determinations of viruria (urine viral load [UPCR])and viremia (viral load in blood [VLB]) have been proposed as surrogate markers of polyomavirus allograft nephropathy (PVAN). In this study, we present the experience with the concurrent evaluation of UC, UPCR, and VLB in 349 patients (940 sets of samples). Results were correlated with each other and with a previous, concurrent, or subsequent biopsy diagnosis of PVAN. Patients were followed up for a mean of 27 months posttransplantation. We conclude that both UC and UPCR are useful for screening of renal transplant recipients. Simultaneous performance of both UC and UPCR does not add useful clinical information. In patients with positive UC, performance of UPCR, however, can allow for the distinction between BK and JC polyoma viruses. Quantitative measurement of viremia is not indicated in patients lacking viruria because no patients with PVAN present with this combination of findings. In patients with viruria, a positive viremia strongly correlates with PVAN. Rationale selection of screening protocols based on the current knowledge of the infection and tailored to the available laboratory capabilities in each transplantation center can optimize the use of resources.